Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and ...synonyms was performed on November 28.sup.th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters-including serum interleukin-6 levels-from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cells challenged by photosensitized oxidations face strong redox stresses and rely on autophagy to either survive or die. However, the use of macroautophagy/autophagy to improve the efficiency of ...photosensitizers, in terms of inducing cell death, remains unexplored. Here, we addressed the concept that a parallel damage in the membranes of mitochondria and lysosomes leads to a scenario of autophagy malfunction that can greatly improve the efficiency of the photosensitizer to cause cell death. Specific damage to these organelles was induced by irradiation of cells pretreated with 2 phenothiazinium salts, methylene blue (MB) and 1,9-dimethyl methylene blue (DMMB). At a low concentration level (10 nM), only DMMB could induce mitochondrial damage, leading to mitophagy activation, which did not progress to completion because of the parallel damage in lysosome, triggering cell death. MB-induced photodamage was perceived almost instantaneously after irradiation, in response to a massive and nonspecific oxidative stress at a higher concentration range (2 µM). We showed that the parallel damage in mitochondria and lysosomes activates and inhibits mitophagy, leading to a late and more efficient cell death, offering significant advantage (2 orders of magnitude) over photosensitizers that cause unspecific oxidative stress. We are confident that this concept can be used to develop better light-activated drugs.
Abbreviations: ΔΨm: mitochondrial transmembrane inner potential; AAU: autophagy arbitrary units; ATG5, autophagy related 5; ATG7: autophagy related 7; BAF: bafilomycin A
1
; BSA: bovine serum albumin; CASP3: caspase 3; CF: carboxyfluorescein; CTSB: cathepsin B; CVS: crystal violet staining; DCF: dichlorofluorescein; DCFH
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: 2ʹ,7ʹ-dichlorodihydrofluorescein; DMMB: 1,9-dimethyl methylene blue; ER: endoplasmic reticulum; HaCaT: non-malignant immortal keratinocyte cell line from adult human skin; HP: hydrogen peroxide; LC3B-II: microtubule associated protein 1 light chain 3 beta-II; LMP: lysosomal membrane permeabilization; LTG: LysoTracker™ Green DND-26; LTR: LysoTracker™ Red DND-99; 3-MA: 3-methyladenine; MB: methylene blue; mtDNA: mitochondrial DNA; MitoSOX™: red mitochondrial superoxide probe; MTDR: MitoTracker™ Deep Red FM; MTO: MitoTracker™ Orange CMTMRos; MT-ND1: mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1; MTT: methylthiazolyldiphenyl-tetrazolium bromide;
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O
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: singlet oxygen; OH
.
hydroxil radical; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PBS: phosphate-buffered saline; PI: propidium iodide; PDT: photodynamic therapy; PS: photosensitizer; QPCR: gene-specific quantitative PCR-based; Rh123: rhodamine 123; ROS: reactive oxygen species RTN: rotenone; SQSTM1/p62: sequestosome 1; SUVs: small unilamellar vesicles; TBS: Tris-buffered saline
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The grasshopper Rhammatocerus brasiliensis shows polymorphism of B chromosomes, but the magnitude of B-chromosome occurrence and the factors that may contribute to their dispersion in the species ...remain unknown thus far. The present study analyzed the occurrence and dispersion of B chromosomes in R. brasiliensis individuals from 21 populations widely distributed in the Brazilian Northeast. The genetic connectivity between 10 populations was verified through analysis of ISSR markers from 200 individuals. Of the 21 populations, 19 presented individuals with one B chromosome, three with two, and one with three B chromosomes. The B chromosome is of medium size and constitutive heterochromatin (CH) located in the pericentromeric region. A variant B chromosome was observed in three populations, similar in size to that of chromosome X, gap and CH, and located in the terminal region. B chromosome frequencies in different populations varied from 0% to 18,8%, mean 8,5%. The wide distribution of the B chromosome is likely a consequence of the positive gene flow among the analyzed populations. B-chromosome occurrence in populations of R. brasiliensis possibly follows the population genetic structure of the species and, owing to the existence of a variant, its origin may not be recent.
The richness of marine teleost fishes from the tropical northeastern Brazilian coast was compiled through an extensive search of published species records and of voucher specimens in collections. ...Results are presented in a systematic list that includes 571 marine species across 98 families considered as valid records in coastal and estuarine environments. 516 species (90.4%) are represented by voucher specimens in collections. Species reported in the literature with pending confirmation, or known only from vouchers, may add 72 species to the list, 18 of them without previous mention in the literature representing new records for the study region. Brazilian endemic species are also reported, seven of which are exclusive to the northeastern coast. Additionally, 91 species belonging to 41 families are treated as erroneous or doubtful records for the region, and their geographic distribution or taxonomic status commented upon. Among the valid species recorded, 21 are listed as threatened according to the IUCN Red List and 24 by the Brazilian official list of threatened species. At least four species introduced in the Western Atlantic are now considered invasive in northeastern Brazil. The data presented herein result from the most comprehensive survey of the coastal marine ichthyofauna of northeastern Brazil. It adds 154 species records when compared to the maximum species richness previously reported for the study region in a single publication and serves as a baseline to promote future studies in fish systematics, biogeography, ecology and conservation. Notwithstanding, the species richness of this region remains an underestimate pending additional taxonomic research and the availability of online data for regional collections.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
An artificial diet to mass-rear Euschistus heros (F. 1798) (Hemiptera: Pentatomidae) was developed in the laboratory. Biological studies were conducted under controlled conditions of temperature (25 ...± 2 °C), RH: 60 ± 10%, and photoperiod of 14:10 (L:D) h. Out of 13 diets tested, 2 diets (D9 and D11) were the most suitable. The artificial diets selected had the same composition (green beans, peanuts, sucrose, water, Nipagin, and sorbic acid) except for different antimicrobial agents (D11 has tetracycline, and D9 doesn't). The 68% viability for the egg-adult period of insects reared on these lyophilized artificial diets (LAD) was almost twice as high as the 38% viability obtained with the natural diet. Although adults reared on LAD weighed 17% less than those reared on the natural diet, mean fecundity was higher than on the natural diet (282 eggs/female), reaching 430 eggs/female. The net reproductive rate (Ro) increased over the generations for the diets with lyophilized material and antimicrobial agents. The opposite occurred with the diet of lyophilized material without antimicrobial agents, showing that the insects either adapted or degenerated through generations. Lyophilized diets supported the production of E. heros through at least 10 generations, with no degeneration.
SUMMARY
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The antinociceptive effect of risedronate in experimental pain models in rats and mice was investigated in the present study.
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Rats received zymosan intra‐articularly (i.art.) into the ...right knee joint and the nociceptive response was assessed using the articular incapacitation test. Joint washouts were used for determining cell influx, tumour necrosis factor (TNF)‐α and leukotriene (LT) B4 levels.
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Mice received either zymosan (1 mg) or acetic acid (0.6%) i.p. and the nociceptive response was measured as the number of writhings between 0 and 30 min after the stimuli. Control animals received i.p. injections of saline.
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Groups were pretreated with risedronate (5–500 µg/kg, s.c.) and compared with vehicle (saline)‐treated (NT) animals. One group of rats was cotreated with the µ‐opioid receptor antagonist naloxone (2 mg/kg, s.c.) prior to risedronate, followed by 1 mg zymosan i.art.
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Risedronate, at 100 and 500 µg/kg, significantly and dose‐dependently inhibited the nociceptive response in the writhings test (P < 0.05), inhibiting responses to acetic acid by 65.4 and 49.2%, respectively, and to zymosan by 72.9 and 71.9%, respectively.
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Pretreatment with risedronate also significantly (P < 0.05) and dose‐dependently inhibited the articular incapacitation in zymosan‐arthritis.
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Risedronate, at 50 µg/kg, significantly inhibited TNF‐α release as compared with the NT group (39.4 ± 9.8 vs 145.6 ± 43.3 pg/mL TNF‐α, respectively).
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Risedronate, at 50 and 100 µg/kg, significantly inhibited LTB4 release into the joints compared with the NT group (2883.1 ± 73.2, 1911.5 ± 205.3 and 4709.9 ± 237.2 pg/mL, respectively). These effects of risedronate were associated with a significant reduction in the inflammatory cell infiltration.
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Cotreatment with risedronate and naloxone did not reverse the antinociceptive effects of risedronate in zymosan‐arthritis.
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This is the first demonstration that risedronate displays intrinsic antihypernociceptive activity. This effect is associated with reduced cell infiltration and inhibition of TNF‐α and LTB4 release and is not linked to an endogenous opioid‐release mechanism.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
In this study, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) with germanium crystals was used to characterize the acrylonitrile content (ACN) of nitrile rubber (NBR) ...filled with carbon black after undergoing thermal and chemical degradations. Five NBR/carbon black formulations with ACN contents ranging from 29.7 to 45.4% were prepared. The mechanical and chemical properties of the NBR compounds were determined before and after exposure at 120 °C for 7, 15, 30, 60, and 90 days in the following environments: thermo-oxidative and simulated production fluid Type A.1.ii specified in ISO 23936-2:2011. A linear model with an R-squared statistic of 99.6% and a correlation coefficient of 0.998 was generated using the ATR-FTIR data of the A2237/A967 ratio of unaged NBR compounds and the actual value of the acrylonitrile content of neat NBR elastomers determined by 13-carbon nuclear magnetic resonance spectroscopy. This model was used to estimate the acrylonitrile content of degraded NBR compounds. The times that caused severe degradation of NBR compounds in thermo-oxidative and simulated production fluid environments were 15–30 days and 30–90 days, respectively. The ACN contents of those aged NBR compounds were successfully estimated using ATR-FTIR experimental values applied to the linear fit model of unaged NBR/carbon black compounds. This made it possible to differentiate between compounds with high and low ACN content, despite the high level of degradation. Thus, the ATR-FTIR technique combined with statistical tools can be a useful tool to predict the service life of rubber products and other composite materials.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific ...receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?synthesis.In this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two axes.The first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases.In this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal syndrome.The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.
Abstract Probiotic bacteria inclusion on fruit pulp is an exceptional alternative for the production and innovation of functional foods. Therefore, the present work aims to study the drying of Caja ...(Spondias mombin) pulp added with Bifidobacterium animalis ssp. lactis using a spouted bed. An experimental design comprising 11 experiments was used on the drying, varying the inlet temperature (50 ºC, 60 ºC, and 70 ºC), the maltodextrin concentration (2.5, 5.0, and 7.5% wt) and inulin concentration (2.5, 5.0, and 7.5% wt). The dependent variables studied in our work were the process yield and the number of viable cells. The liquid fruit pulp presented physicochemical conditions for bacteria growth and high content of bioactive compounds. Results revealed that lower inlet temperature in combination with lower concentrations of maltodextrin and inulin resulted in a powder with a higher number of viable cells. Even though temperature degradation is a critical factor for product quality while using drying processes, it was considered that the process was efficient because of the high cell viability, which is the critical factor to consider the product as probiotic.