Paclitaxel is an antineoplastic agent widely used to treat several solid tumor types. The primary mechanism of action of paclitaxel is based on microtubule stabilization inducing cell-cycle arrest. ...Here, we use several tumor models to show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes antitumor immunity.
, paclitaxel reprogrammed M2-polarized macrophages to the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel also modulated the tumor-associated macrophage (TAM) profile in mouse models of breast and melanoma tumors; gene expression analysis showed that paclitaxel altered the M2-like signature of TAMs toward an M1-like profile. In mice selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre
/TLR4
), the antitumor effect of paclitaxel was attenuated. Gene expression analysis of tumor samples from patients with ovarian cancer before and after treatment with paclitaxel detected an enrichment of genes linked to the M1 macrophage activation profile (IFNγ-stimulated macrophages). These findings indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4, which might contribute to the antitumor effect of paclitaxel and provide a rationale for new combination regimens comprising paclitaxel and immunotherapies as an anticancer treatment.
This study provides new evidence that the antitumor effect of paclitaxel occurs in part via reactivation of the immune response against cancer, guiding tumor-associated macrophages toward the M1-like antitumor phenotype.
http://cancerres.aacrjournals.org/content/canres/78/20/5891/F1.large.jpg
.
To assess the effects of clinical-like cryotherapy on inflammatory signs (in vivo neutrophil migration, cytokines, and joint inflammation), pain, joint swelling, balance, and motor coordination in ...mice with knee arthritis. Young C57BL/6 mice were randomly divided into three groups (8 to 10 mice per group): Control group: mice with no intervention; antigen-induced arthritis (AIA) group: mice sensitized and immunized with intra-articular (i.a.) injection of methylated bovine serum albumin (mBSA); and AIA + cryotherapy group: mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol. After 21 days of sensitization, AIA and AIA + cryotherapy groups received i.a. injection of mBSA (100 μg/joint) to induce joint inflammation, and a clinical-like cryotherapy protocol was applied to AIA + cryotherapy group (crushed ice bag, two cryotherapy sessions of 20 min every two hours). Experimental analysis was conducted in the initial (immediately after i.a. injection of mBSA) and final periods (two hours after the second cryotherapy session). The number of synovial fluid neutrophils, cytokine levels, joint histology, pain, joint swelling, and motor performance were also analyzed. Our results showed that clinical-like cryotherapy in mice with acute knee arthritis reduced inflammatory signs, pain, and joint swelling, and improved balance and motor coordination.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuroimmune-glia interactions have been implicated in the development of neuropathic pain. Interleukin-27 (IL-27) is a cytokine that presents regulatory activity in inflammatory conditions of the ...central nervous system. Thus, we hypothesized that IL-27 would participate in the neuropathic pain process. Here, we found that neuropathic pain caused by peripheral nerve injury (spared nerve injury model; SNI), was enhanced in IL-27-deficient
mice, whereas nociceptive pain is similar to that of wild-type mice. SNI induced an increase in the expression of IL-27 and its receptor subunit (
) in the sensory ganglia and spinal cord. IL-27 receptor was expressed mainly in resident macrophage, microglia, and astrocytes of the sensory ganglia and spinal cord, respectively. Finally, we identify that the antinociceptive effect of IL-27 was not observed in IL-10
mice. These results provided evidence that IL-27 is a cytokine produced after peripheral nerve injury that counteracts neuropathic pain development through induction of the antinociceptive cytokine IL-10. In summary, our study unraveled the role of IL-27 as a regulatory cytokine that counteracts the development of neuropathic pain after peripheral nerve damage. In conclusion, they indicate that immunotherapies based on IL-27 could emerge as possible therapeutic approaches for the prevention of neuropathic pain development after peripheral nerve injury.
The catalytic conversion of glycerol to acrolein by liquid-phase dehydration over molecular sieves catalysts was studied. In order to understand the role of the acidity, structure and porosity, five ...structures were synthesized and evaluated. The lower the Si/Al ratio, the higher the activity; large pore molecular sieves, as HY showed high performance (conversion
=
89.0%; selectivity to acrolein
=
99.5%), while siliceous molecular sieves such as SBA-15 possessing weak acidity, exhibited low conversion (40.6%) and decreased selectivity to acrolein (84.0%). The structure and the acidity govern the selectivity to acrolein and hydroxyacetone, the latter being a by-product mainly dependent on the amount of weak and medium strengths acidic sites, as in the case of Hβ. The activity has almost the same order of the acidity: HY
>
Hβ
>
Mor
>
SBA-15
>
ZSM-23. Modifications of the most acidic and active catalysts by silanation (CVD) or Pt incorporation did not result in an enhanced conversion. The studies of reusability and the nature of the coke deposits indicated that heavy polycondensed and cyclic C
6 compounds resulting from the reaction between glycerol and acrolein block the pores and the acidic sites. The blockage was the main cause of deactivation, whereas acidic site poisoning led to a less extensive deactivation of the surface active sites. From these results, it was possible to establish acidity–activity–deactivation relationships that allow to explain the behaviour of the catalysts.
Background
Paclitaxel (PCX) is the first‐line choice for the treatment of several types of cancer, including breast, ovarian, and lung cancers. However, patients who receive even a single dose with ...PCX commonly develop mechanical and cold allodynia, a symptom known as PCX‐associated acute pain syndrome (P‐APS). Here, we assessed possible involvement of kinin–kallikrein and renin‐angiotensin systems in P‐APS in mice.
Methods
Male mice C57Bl/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1−/−) and B2 (B2−/−), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P‐APS was induced by administration of PCX 4 mg/kg, i.v.. ACE inhibitors (captopril and enalapril), antagonists for angiotensin II type 1 (losartan) and type 2 (AT2R; PD123319 and EMA 401) receptors were administrated prior the treatment with PCX. RT‐PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors.
Results
Administration of PCX in B1−/− and B2−/− mice induced lower mechanical and cold allodynia compared to the WT. However, the pre‐treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P‐APS. Surprisingly, we found that mice pre‐treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX.
Conclusion
Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P‐APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P‐APS in humans.
Significance
Kinin–kallikrein and renin‐angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel‐associated acute pain syndrome (P‐APS) in mice. Antagonists for AT2R are potential alternatives to prevent P‐APS.
The VISCACHA survey – I. Overview and first results Maia, Francisco F S; Dias, Bruno; Santos, João F C ...
Monthly notices of the Royal Astronomical Society,
04/2019, Letnik:
484, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
The VISCACHA (VIsible Soar photometry of star Clusters in tApii and Coxi HuguA) Survey is an ongoing project based on deep photometric observations of Magellanic Cloud star clusters, ...collected using the SOuthern Astrophysical Research (SOAR) telescope together with the SOAR Adaptive Module Imager. Since 2015 more than 200 h of telescope time were used to observe about 130 stellar clusters, most of them with low mass (M < 104 M⊙) and/or located in the outermost regions of the Large Magellanic Cloud and the Small Magellanic Cloud. With this high-quality data set, we homogeneously determine physical properties from statistical analysis of colour–magnitude diagrams, radial density profiles, luminosity functions, and mass functions. Ages, metallicities, reddening, distances, present-day masses, mass function slopes, and structural parameters for these clusters are derived and used as a proxy to investigate the interplay between the environment in the Magellanic Clouds and the evolution of such systems. In this first paper we present the VISCACHA Survey and its initial results, concerning the SMC clusters AM3, K37, HW20, and NGC 796 and the LMC ones KMHK228, OHSC3, SL576, SL61, and SL897, chosen to compose a representative subset of our cluster sample. The project’s long-term goals and legacy to the community are also addressed.
Gas gangrene in mammals: a review Junior, Carlos A. Oliveira; Silva, Rodrigo O. S.; Lobato, Francisco C. F. ...
Journal of veterinary diagnostic investigation,
03/2020, Letnik:
32, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Gas gangrene is a necrotizing infection of subcutaneous tissue and muscle that affects mainly ruminants and horses, but also other domestic and wild mammals. Clostridium chauvoei, C. septicum, C. ...novyi type A, C. perfringens type A, and C. sordellii are the etiologic agents of this disease, acting singly or in combination. Although a presumptive diagnosis of gas gangrene can be established based on clinical history, clinical signs, and gross and microscopic changes, identification of the clostridia involved is required for confirmatory diagnosis. Gross and microscopic lesions are, however, highly suggestive of the disease. Although the disease has a worldwide distribution and can cause significant economic losses, the literature is limited mostly to case reports. Thus, we have reviewed the current knowledge of gas gangrene in mammals.
Core collections are of strategic importance as they allow the use of a small part of a germplasm collection that is representative of the total collection. The objective of this study was to develop ...a soybean core collection of the USDA Soybean Germplasm Collection by comparing the results of random, proportional, logarithmic, multivariate proportional and multivariate logarithmic sampling strategies. All but the random sampling strategy used stratification of the entire collection based on passport data and maturity group classification. The multivariate proportional and multivariate logarithmic strategies made further use of qualitative and quantitative trait data to select diverse accessions within each stratum. The 18 quantitative trait data distribution parameters were calculated for each core and for the entire collection for pairwise comparison to validate the sampling strategies. All strategies were adequate for assembling a core collection. The random core collection best represented the entire collection in statistical terms. Proportional and logarithmic strategies did not maximize statistical representation but were better in selecting maximum variability. Multivariate proportional and multivariate logarithmic strategies produced the best core collections as measured by maximum variability conservation. The soybean core collection was established using the multivariate proportional selection strategy.
Objective
To compare the unilateral signs of knee osteoarthritis (KOA) 30 and 60 days after anterior cruciate ligament transection (ACLT). Pain, gait function, synovial fluid inflammation, and ...histopathological changes in the synovial membrane were analyzed, as well as the interaction between the variables.
Materials and methods
Male
Wistar
rats (
n
= 32; 219.2 ± 18.6 g) were randomly distributed into four groups of eight animals each. Two groups were submitted to unilateral ACLT surgery to induce KOA and analyzed after 30 (KOA30) and 60 days (KOA60). Two control groups (without surgery) were also assessed after the same time periods (C30 and C60). All the groups were evaluated before ACLT from the least to most stressful tests (skin temperature, mechanical response threshold, gait test, thermal response threshold, and joint swelling), as well as 30 and 60 days after surgery. After euthanasia, the synovial fluid and synovial membrane were collected.
Results
Thirty days after ACLT, KOA30 showed decrease paw print area and mechanical response threshold, higher joint swelling, skin temperature, leukocyte count, cytokine levels, and synovitis score. No differences were found between KOA30 and KOA60.
Conclusion
Our data showed that 30 days after ACLT is sufficient to induce signs of KOA in rats, such as pain, functional impairment, and synovial inflammation, suggesting that a shorter time period can be used as an experimental model.
Saturated monocarboxylic fatty acids with long carbon chains are organic compounds widely used in several applied fields, such as energy production, thermal energy storage, antibactericidal, ...antimicrobial, among others. In this research, a new polymorphic phase of arachidic acid (AA) crystal was synthesized and its structural and vibrational properties were studied by single-crystal X-ray diffraction (XRD) and polarized Raman scattering. The new structure of AA was solved at two different temperature conditions (100 and 300 K). XRD analysis indicated that this polymorph belongs to the monoclinic space group
P
2
1
/
c
(
C
2h
5
), with four molecules per unit cell (
Z
= 4). All molecules in the crystal lattice adopt a
gauche
configuration, exhibiting a
R
2
2
(8) hydrogen bond pattern. Consequently, this new polymorphic phase, labeled as B form, is a polytype belonging to the monoclinic symmetry,
i.e
., B
m
form. Complementarily, Hirshfeld's surfaces were employed to analyze the intermolecular interactions within the crystal lattice of this polymorph at temperatures of 100 and 300 K. Additionally, density functional theory (DFT) calculations were performed to assign all intramolecular vibration modes related to experimental Raman-active bands, which were properly calculated using a dimer model, considering a pair of AA molecules in the
gauche
configuration, according to the solved-crystal structure.
A new polymorphic phase of arachidic acid crystal, and its structure, intermolecular interactions, and vibrational properties.
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