Isolation and characterization of anti-inflammatory and immunomodulatory compounds from higher plants

Autoimmunity is a pathological chronic inflammatory state that arises when the immune system mistakenly targets healthy cells and tissues in the human body. Clinically, there are more than 80 types of autoimmune diseases described, including well-known conditions like psoriasis, rheumatoid arthritis, type I diabetes, multiple sclerosis, and Crohn’s disease. The incidence of autoimmune diseases in the human population is around 5−10% and continues to rise. Although current treatment options with immunosuppressant drugs like cyclosporine or biologic agents have shown excellent efficacy, they are often associated with unwanted side effects such as increased susceptibility to infections and malignancies, drug-drug interactions, cytokine release syndrome, hypersensitivity reactions, or anti-drug antibodies. Additionally, current drugs often lose efficacy over time, which leads to non-responsiveness, or to a lack of long-lasting relief of symptoms. Finally, the treatment of autoimmune diseases is very expensive and generates high treatment costs. Thus, there is a need for continued research into new therapies. In the pathogenesis of chronic inflammation and autoimmune diseases enhanced activation and proliferation of T cells plays a crucial role. To address this issue, targeted therapies that specifically enhance inhibitory pathways in T cells are an attractive approach to treat human autoimmune diseases. Thus, the first aim of this study was to discover novel immune-modulating substances from plant extracts that specifically inhibit human T cell activation and proliferation. To achieve this goal, an in-house library of 600 extracts from plants endemic to Panama was screened for potential T cell inhibition. As one of the hits, an ethyl acetate extract from the aerial parts of Hyptis brachiata Briq. (Lamiaceae) was found to have strong inhibitory effects on T cell activation and proliferation. Seven aryltetralin lignans, five arylnaphthalene lignans, two flavonoids, three triterpenes, and cinnamyl cinnamate were isolated using an HPLC-based activity profiling approach. The aryltetralin lignans inhibited T cell proliferation in a concentration-dependent manner without inducing apoptosis. Additionally, the ethyl acetate extract and isolated triterpenes weakly lowered the secretion of inflammatory cytokines like IL-2 and TNF-α by activated T cells. The suppressive effects on activated T cells could be attributed to a synergistic interplay between the aryltetralin lignans and triterpenes. These findings suggest that the extract from Hyptis brachiata could be further investigated as a potential treatment for T cell-mediated inflammatory and autoimmune diseases. The findings of this study have been published in Biomedicine & Pharmacotherapy, 160 in 2023. Another aspect of this work aimed to explore the potential use of saffron corms (Crocus sativus L., Iridaceae) that arise as a waste product from saffron cultivation. A 70% ethanol extract of the corms and a sugar-depleted methanol fraction of the extract have been found to inhibit the TNF-α/IFN-γ-induced gene expression and secretion of the chemokines IL-8, MCP-1, and RANTES in human HaCaT keratinocytes. The effects were in part stronger than those of the positive control hydrocortisone. These chemokines are responsible for monocyte and T cell attraction, as well as for keratinocyte proliferation, making them critical in wound healing and in the development of inflammatory skin diseases like psoriasis and atopic dermatitis. A series of unusual bidesmosidic glycosides of echinocystic acid, which bear a 3,16-dihydroxy-10-oxohexadecanoic acid residue attached to the glycosidic moiety at C-28, were isolated using centrifugal partition chromatography and different C18 and HILIC HPLC stationary phases. Two previously reported compounds, azafrines 1 and 2, and eight new congeners named as azafrines 3−10 were identified. Saffron saponins significantly inhibited TNF-α/IFN-γ-induced secretion of RANTES in human HaCaT cells at 1 μM (p < 0.001). In vitro data suggest that saffron saponins possess anti-inflammatory properties by affecting the expression and secretion of chemotactic cytokines, and could therefore potentially be used as topical agents for treating inflammatory skin diseases. These results have been published in the Journal of Natural Products, 84, 2021. The treatment of wounds is an increasingly important challenge, particularly in the case of chronic wounds associated with complex pathophysiology that may arise from autoimmune diseases such as psoriasis or type I diabetes. These wounds reduce the quality of life of many patients and current wound healing therapies are only partially effective. The lack of effective treatments for non-healing chronic wounds has become a growing clinical concern, and ongoing research is focused on obtaining more effective options to reduce treatment costs, provide long-term relief, and facilitate effective scar healing. Historically, medicinal plants have been successfully used in wound treatment, and today they remain widely applied. Plant-based products have gained increasing interest as cost-efficient treatment options for wounds, as they represent mixtures of various phytochemicals that could act beneficially in a synergistic manner during the complex wound healing process. In this context, the last project described in this work investigated the wound healing properties of Teucrium polium subsp. capitatum (L.) Arcang (syn. Teucrium capitatum L.; Lamiaceae), a plant traditionally used in Algeria as a decoction or ointment to treat hypertension, diabetes, and wounds. Initially, a wound excision model in rabbits confirmed beneficial wound healing effects of a methanol extract from the aerial parts of T. polium. An ointment prepared from the T. polium extract demonstrated significant wound healing properties, superior to those of the reference drug Cicatryl-Bio containing allantoin as the active ingredient. A comprehensive analysis by HPLC-PDA-ESIMS led to the isolation and identification of 12 flavonoids and two phenylethanoid glycosides as the main constituents of the extract. Further investigation led to the isolation of six acetoxylated neo-clerodane diterpenes, including 20-acetylauropolin and 6-acetylteucjaponin A, along with four previously undescribed congeners. Some of the isolated diterpenes possess unusual structural features in the class of neo-clerodane diterpenes, such as a rare C-20 acetal function that forms an oxepane ring to C-7 of the trans-decalin core structure. The beneficial wound healing effect of T. polium is thought to be due to the combined effects of its polyphenolic constituents. Overall, the data support the use of T. polium as a wound healing agent in Algerian traditional medicine. The results have been published in the South African Journal of Botany, 137, 2021, and the Journal of Molecular Structure, 1284, 2023. In conclusion, various approaches have been employed to investigate plant extracts and their secondary metabolites in the context of T cell-mediated autoimmunity, inflammatory skin diseases, such as psoriasis and atopic dermatitis, and wound healing. These diseases are challenging to treat due to their complex pathophysiology, involving numerous mechanisms and targets. However, plants, with their complex mixtures of phytochemical substances, can exert their effects on various targets, offering a potential advantage in treating multifactorial diseases. Complementary modes of action from structurally diverse substance classes may act synergistically on different target cell types or proteins, contributing to improved clinical outcomes. Therefore, preparations containing various phytochemical substances from plant extracts may have the potential as alternative treatment options for these complex disorders. This work provides insights into how extracts and pure substances from H. brachiata, C. sativus, and T. polium may exert beneficial effects in the treatment of multifactorial conditions such as T cell-mediated autoimmunity, inflammatory skin diseases, and wound healing

Non-Compact Pure Gauge QED in 3D is Free

For all Poincar\'e invariant Lagrangians of the form ${\cal L}\equiv f(F_{\mu\nu})$, in three Euclidean dimensions, where $f$ is any invariant function of a non-compact $U(1)$ field strength $F_{\mu\nu}$, we find that the only continuum limit (described by just such a gauge field) is that of free field theory: First we approximate a gauge invariant version of Wilson's renormalization group by neglecting all higher derivative terms $\sim \partial^nF$ in ${\cal L}$, but allowing for a general non-vanishing anomalous dimension. Then we prove analytically that the resulting flow equation has only one acceptable fixed point: the Gaussian fixed point. The possible relevance to high-$T_c$ superconductivity is briefly discussed.Comment: 11 pages, plain tex, uses harvmac. Minor additions - version to be published in Physics Letters

Thermal Decomposition of the Murchison CM2 Carbonaceous Chondrite: Implications of Space Weathering Processes for Sample Return Missions

Primitive carbonaceous asteroids are the target bodies for the JAXA Hayabusa2 mission to Ryugu and the NASA OSIRIS-REx mission to Bennu. Both asteroids share spectral characteristics of CI/CM type carbonaceous chondrites. Ryugu, in particular, appears to have undergone thermal processing that has modified its spectral properties. The nature and extent of space weathering processes on the surfaces of Bennu and Ryugu are under active investigation using remote sensing data from the missions [4] and through laboratory studies on analog materials. The analog studies are needed in order to understand the mineralogical and chemical changes that occur in space weathered samples that give rise to the observed optical effects measured by remote-sensing and to prepare for the analysis of returned samples. The space weathering effects of micrometeorite impact and solar wind irradiation on primitive carbonaceous chondrites have been simulated by analog studies on the Murchison CM2 chondrite. We performed a coordinated mineralogical, chemical and spectroscopic study to examine in detail the effects of thermal metamorphism on Murchison samples as an analog to processes that may have occurred on Ryugu. The bulk measurements including X-ray diffraction (XRD), Mssbauer spectroscopy, UV-VIS-NIR spectroscopy, thermogravimetric analysis, and evolved gas analysis are reported in a companion paper. Here we report on our preliminary nanoscale mineralogical and chemical analyses of pre- and post-heated Murchison samples using multiple electron beam techniques to understand how the mineralogical, chemical, and physical characteristics of carbonaceous chondrites change with increasing thermal effects

Renormalization of composite operators

The blocked composite operators are defined in the one-component Euclidean scalar field theory, and shown to generate a linear transformation of the operators, the operator mixing. This transformation allows us to introduce the parallel transport of the operators along the RG trajectory. The connection on this one-dimensional manifold governs the scale evolution of the operator mixing. It is shown that the solution of the eigenvalue problem of the connection gives the various scaling regimes and the relevant operators there. The relation to perturbative renormalization is also discussed in the framework of the $\phi^3$ theory in dimension $d=6$.Comment: 24 pages, revtex (accepted by Phys. Rev. D), changes in introduction and summar

Exact Renormalization Group Equations. An Introductory Review

We critically review the use of the exact renormalization group equations (ERGE) in the framework of the scalar theory. We lay emphasis on the existence of different versions of the ERGE and on an approximation method to solve it: the derivative expansion. The leading order of this expansion appears as an excellent textbook example to underline the nonperturbative features of the Wilson renormalization group theory. We limit ourselves to the consideration of the scalar field (this is why it is an introductory review) but the reader will find (at the end of the review) a set of references to existing studies on more complex systems.Comment: Final version to appear in Phys. Rep.; Many references added, section 4.2 added, minor corrections. 65 pages, 6 fig

BRS symmetry for Yang-Mills theory with exact renormalization group

In the exact renormalization group (RG) flow in the infrared cutoff $\Lambda$ one needs boundary conditions. In a previous paper on $SU(2)$ Yang-Mills theory we proposed to use the nine physical relevant couplings of the effective action as boundary conditions at the physical point $\Lambda=0$ (these couplings are defined at some non-vanishing subtraction point $\mu \ne 0$). In this paper we show perturbatively that it is possible to appropriately fix these couplings in such a way that the full set of Slavnov-Taylor (ST) identities are satisfied. Three couplings are given by the vector and ghost wave function normalization and the three vector coupling at the subtraction point; three of the remaining six are vanishing (\eg the vector mass) and the others are expressed by irrelevant vertices evaluated at the subtraction point. We follow the method used by Becchi to prove ST identities in the RG framework. There the boundary conditions are given at a non-physical point $\Lambda=\Lambda' \ne 0$, so that one avoids the need of a non-vanishing subtraction point.Comment: 22 pages, LaTeX style, University of Parma preprint UPRF 94-41

X-Ray Diffraction and Reflectance Spectroscopy of Murchison Powders (CM2) After Thermal Analysis Under Reducing Conditions to Final Temperatures Between 300 and 1300c

The asteroids Ryugu and Bennu have spectral characteristics in common with CI/CM type carbonaceous chondrites and are target bodies for JAXAs Hayabusa2 and NASAs OSIRIS-Rex missions, respectively. Analog studies, based primarily on the Murchison CM2 chondrite, provide a pathway to separate spectral properties resulting space weathering from those inherent to parent-body, mineralogy, chemistry, and processes. Ryugu shares spectral properties with thermally metamorphosed and partly dehydrated CI/CM chondrites. We have undertaken a multidisciplinary study of the thermal decomposition of Murchison powder samples as an analog to metamorphic process that may have occurred on Ryugu. Bulk analyses include thermal And evolved gas analysis, X-ray diffraction (XRD), and VIS-NIR and Mssbauer spectroscopy; micro- to nanoscale analyses included scanning and transmission electron microscopy and electron probe micro analysisWe report here XRD and VIS-NIR analyses of pre- and post-heated Murchison powders, and in a companion paper report results from multiple electron beam techniques

SiS in the circumstellar envelope of IRC +10126: maser and quasi-thermal emission

We present new Effelsberg-100 m, ATCA, and VLA observations of rotational SiS transitions in the circumstellar envelope (CSE) of IRC +10216. Thanks to the high angular resolution achieved by the ATCA observations, we unambiguously confirm that the molecule's J=1-0 transition exhibits maser action in this CSE, as first suggested more than thirty years ago. The maser emission's radial velocity peaking at a local standard of rest velocity of -39.862$\pm$0.065 km/s indicates that it arises from an almost fully accelerated shell. Monitoring observations show time variability of the SiS (1-0) maser. The two lowest-$J$ SiS quasi-thermal emission lines trace a much more extended emitting region than previous high-J SiS observations. Their distributions show that the SiS quasi-thermal emission consists of two components: one is very compact (radius<1.5", corresponding to <3$\times 10^{15}$ cm), and the other extends out to a radius >11". An incomplete shell-like structure is found in the north-east, which is indicative of existing SiS shells. Clumpy structures are also revealed in this CSE. The gain of the SiS (1-0) maser (optical depths of about -5 at the blue-shifted side and, assuming inversion throughout the entire line's velocity range, about -2 at the red-shifted side) suggests that it is unsaturated. The SiS (1-0) maser can be explained in terms of ro-vibrational excitation caused by infrared pumping, and we propose that infrared continuum emission is the main pumping source.Comment: Accepted for publication in ApJ. A high-resolution version can be found at https://gongyan2444.github.io/pdf/cw-leo-sis.pdf 3D movies of SiS cubes can be found at https://gongyan2444.github.io/movie/sis10-3d.avi and https://gongyan2444.github.io/movie/sis21-3d.av

Lunar resources: Oxygen from rocks and soil

The first set of hydrogen reduction experiments to use actual lunar material was recently completed. The sample, 70035, is a coarse-grained vesicular basalt containing 18.46 wt. percent FeO and 12.97 wt. percent TiO2. The mineralogy includes pyroxene, ilmenite, plagioclase, and minor olivine. The sample was crushed to a grain size of less than 500 microns. The crushed basalt was reduced with hydrogen in seven tests at temperatures of 900-1050 C and pressures of 1-10 atm for 30-60 minutes. A capacitance probe, measuring the dew point of the gas stream, was used to follow reaction progress. Experiments were also conducted using a terrestrial basalt similar to some lunar mare samples. Minnesota Lunar Simulant (MLS-1) contains 13.29 wt. percent FeO, 2.96 wt. percent Fe2O3, and 6.56 wt. percent TiO2. The major minerals include plagioclase, pyroxene, olivine, ilmenite, and magnetite. The rock was ground and seived, and experiments were run on the less than 74- and 500-1168-micron fractions. Experiments were also conducted on less than 74-micron powders of olivine, pyroxene, synthetic ilmenite, and TiO2. The terrestrial rock and mineral samples were reduced with flowing hydrogen at 1100 C in a microbalance furnace, with reaction progress monitored by weight loss. Experiments were run at atmospheric pressure for durations of 3-4 hr. Solid samples from both sets of experiments were analyzed by Mossbauer spectroscopy, petrographic microscopy, scanning electron microscopy, tunneling electron microscopy, and x-ray diffraction. Apollo 17 soil 78221 was examined for evidence of natural reduction in the lunar environment. This sample was chosen based on its high maturity level (I sub s/FeO = 93.0). The FeO content is 11.68 wt. percent and the TiO2 content is 3.84 wt. percent. A polished thin section of the 90-150 micron size fraction was analyzed by petrographic microscopy and scanning electron microscopy

(Non) Gauge Invariance of Wilsonian Effective Actions in (Supersymmetric) Gauge Theories : A Critical Discussion

We give a detailed critical discussion of the properties of Wilsonian effective actions, defined by integrating out all modes above a given scale $\mu$. In particular, we provide a precise and relatively convenient prescription how to implement the infrared cutoff $\mu$ in any loop integral that is manifestly Lorentz invariant and also preserves global linear symmetries such as e.g. supersymmetry. We discuss the issue of gauge invariance of effective actions in general and in particular when using background field gauge. Our prescription for the IR cutoff (as any such prescription) breaks the gauge symmetry. Using our prescription, we have explicitly computed, at one loop, many terms of the Wilsonian effective action for general gauge theories, involving bosonic and fermionic matter fields of arbitrary masses and in arbitrary representations, exhibiting the non-gauge invariant (as well as the gauge invariant) terms. However, for supersymmetric gauge theories all non-gauge invariant terms cancel within each supermultiplet. This is strong evidence that in supersymmetric gauge theories this indeed defines a Lorentz, susy and gauge invariant Wilsonian effective action. As a byproduct, we obtain the explicit one-loop Wilsonian couplings for all higher-derivative terms $F D^{2n}F$ in the effective action of arbitrary supersymmetric gauge theories.Comment: 39 pages, 3 figures; several comments in sect. 2.6 and references are adde