-
Pharmaceuticals (Basel, Switzerland) Jun 2024Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect.... (Review)
Review
Acne vulgaris is a common disease, which occurs in adolescents as well as adults and has a significant influence on the patient's quality of life (QoL) in every aspect. Due to resistance to standard therapies, it has become necessary to prospect for new treatment strategies. It is important to highlight that the diagnosis and treatment of the underlying cause of acne such as metabolic and hormonal disorders may significantly improve the effectiveness of acne treatment. The correlation between Insulin Resistance (IR) and acne has been proven. Both disorders share many common occurrence factors and activation pathways. Metformin, an antihyperglycemic agent, seems to be a possible therapy option, not only because of its insulin sensitizing ability but also via plenty of additional effects of this medicine. While the efficiency of metformin therapy in patients with acne and Polycystic Ovary Syndrome (PCOS) is well explored, it is still necessary to evaluate it in patients without any endocrinopathies. This meta-analysis aimed to estimate the effectiveness of oral metformin as a monotherapy in acne patients without PCOS or other endocrinopathies. Study selection was performed with included criteria such as no PCOS and other endocrinopathies diagnosed, oral administration of metformin, and metformin in monotherapy. Selected studies contained comparisons in the Global Acne Grading System (GAGS) before and after metformin therapy. Statistical analysis detected significant improvement in skin condition after treatment with metformin.
PubMed: 38931395
DOI: 10.3390/ph17060728 -
Nutrients Jun 2024Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies... (Review)
Review
Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD is a unique autoimmune condition, as it is the only one in which the environmental trigger is known: gluten, a storage protein present in wheat, barley, and rye. How and when the loss of tolerance of the intestinal mucosa to gluten occurs is still unknown. This event, through the activation of adaptive immune responses, enhances epithelial cell death, increases the permeability of the epithelial barrier, and induces secretion of pro-inflammatory cytokines, resulting in the transition from genetic predisposition to the actual onset of the disease. While the role of gastrointestinal infections as a possible trigger has been considered on the basis of a possible mechanism of antigen mimicry, a more likely alternative mechanism appears to involve a complex disruption of the gastrointestinal microbiota ecosystem triggered by infections, rather than the specific effect of a single pathogen on intestinal mucosal homeostasis. Several lines of evidence show the existence of intestinal dysbiosis that precedes the onset of CeD in genetically at-risk subjects, characterized by the loss of protective bacterial elements that both epigenetically and functionally can influence the response of the intestinal epithelium leading to the loss of gluten tolerance. We have conducted a literature review in order to summarize the current knowledge about the complex and in part still unraveled dysbiosis that precedes and accompanies CeD and present some exciting new data on how this dysbiosis might be prevented and/or counteracted. The literature search was conducted on PubMed.gov in the time frame 2010 to March 2024 utilizing the terms "celiac disease and microbiota", "celiac disease and microbiome", and "celiac disease and probiotics" and restricting the search to the following article types: Clinical Trials, Meta-Analysis, Review, and Systematic Review. A total of 364 papers were identified and reviewed. The main conclusions of this review can be outlined as follows: (1) quantitative and qualitative changes in gut microbiota have been clearly documented in CeD patients; (2) intestinal microbiota's extensive and variable interactions with enterocytes, viral and bacterial pathogens and even gluten combine to impact the inflammatory immune response to gluten and the loss of gluten tolerance, ultimately affecting the pathogenesis, progression, and clinical expression of CeD; (3) gluten-free diet fails to restore the eubiosis of the digestive tract in CeD patients, and also negatively affects microbial homeostasis; (4) new tools allowing targeted microbiota therapy, such as the use of probiotics (a good example being precision probiotics like the novel strain of (20220303-A2) begin to show exciting potential applications.
Topics: Celiac Disease; Humans; Gastrointestinal Microbiome; Glutens; Dysbiosis; Intestinal Mucosa
PubMed: 38931237
DOI: 10.3390/nu16121882 -
Plants (Basel, Switzerland) Jun 2024Climate change-induced hazards, such as drought, threaten forest resilience, particularly in vulnerable regions such as the Mediterranean Basin. Maritime pine ( Aiton),...
Climate change-induced hazards, such as drought, threaten forest resilience, particularly in vulnerable regions such as the Mediterranean Basin. Maritime pine ( Aiton), a model species in Western Europe, plays a crucial role in the Mediterranean forest due to its genetic diversity and ecological plasticity. This study characterizes transcriptional profiles of scion and rootstock stems of four graft combinations grown under well-watered conditions. Our grafting scheme combined drought-sensitive and drought-tolerant genotypes for scions (GAL1056: drought-sensitive scion; and Oria6: drought-tolerant scion) and rootstocks (R1S: drought-sensitive rootstock; and R18T: drought-tolerant rootstock). Transcriptomic analysis revealed expression patterns shaped by genotype provenance and graft combination. The accumulation of differentially expressed genes (DEGs) encoding proteins, involved in defense mechanisms and pathogen recognition, was higher in drought-sensitive scion stems and also increased when grafted onto drought-sensitive rootstocks. DEGs involved in drought tolerance mechanisms were identified in drought-tolerant genotypes as well as in drought-sensitive scions grafted onto drought-tolerant rootstocks, suggesting their establishment prior to drought. These mechanisms were associated with ABA metabolism and signaling. They were also involved in the activation of the ROS-scavenging pathways, which included the regulation of flavonoid and terpenoid metabolisms. Our results reveal DEGs potentially associated with the conifer response to drought and point out differences in drought tolerance strategies. These findings suggest genetic trade-offs between pine growth and defense, which could be relevant in selecting more drought-tolerant trees.
PubMed: 38931075
DOI: 10.3390/plants13121644 -
Molecules (Basel, Switzerland) Jun 2024Homogeneous catalysis involving a transition metal agostic interaction (TMHC) is an attractive strategy for C-H bond activation, in which the transition metal agostic...
Homogeneous catalysis involving a transition metal agostic interaction (TMHC) is an attractive strategy for C-H bond activation, in which the transition metal agostic intermediates serve as the critical component. To investigate the roles of manganese agostic intermediates in the unusual migration of the Mn(CO) fragment in the (exo-phenyl)(η-cyclohexenyl)manganese tricarbonyl [(Ph)(η-CH)Mn(CO)] (complex ) under the protonation of tetrafluoroboric acid-diethyl ether (HBF.EtO), a comprehensive density functional theory (DFT) theoretical study was performed. The computational results showed that formation of the [(cyclohex-3-enyl)-η-benzene]manganese tricarbonyl complex [(CH)(η-Ph)Mn(CO)][BF] (complex ) was achieved via a series of mono-agostic and di-agostic intermediates. The overall rate-limiting step for this unusual migration of the Mn(CO) fragment is the formation of the di-agostic (η-phenyl)manganese complex ( → → ) with a Gibbs barrier of 15.4 kcal mol. The agostic intermediates with TMHC agostic interactions were well-characterized by geometry parameters, Atoms-In-Molecules (AIM) analyses, and the Natural Adaptive Orbitals (NAdOs). The located pathways in the current study successfully explained the experimental observations, and the findings on the TMHC agostic interaction provided a new aspect of the catalytic reaction with the manganese complex.
PubMed: 38931010
DOI: 10.3390/molecules29122945 -
Molecules (Basel, Switzerland) Jun 2024L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP)...
L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.
Topics: Humans; Fruit; Cell Line, Tumor; Furocoumarins; Plant Extracts; Ammi; Cell Proliferation; Antineoplastic Agents, Phytogenic; Apoptosis; Chromatography, High Pressure Liquid; Cell Survival
PubMed: 38930940
DOI: 10.3390/molecules29122874 -
Molecules (Basel, Switzerland) Jun 2024This paper investigates the combustion characteristics and pollutant emission patterns of the mixed combustion of lignite (L) and torrefied pine wood (TPW) under...
This paper investigates the combustion characteristics and pollutant emission patterns of the mixed combustion of lignite (L) and torrefied pine wood (TPW) under different blending ratios. Isothermal combustion experiments were conducted in a fixed bed reaction system at 800 °C, and pollutant emission concentrations were measured using a flue gas analyzer. Using scanning electron microscopy (SEM) and BET (nitrogen adsorption) experiments, it was found that torrefied pine wood (TPW) has a larger specific surface area and a more developed pore structure, which can facilitate more complete combustion of the sample. The results of the non-isothermal thermogravimetric analysis show that with the TPW blending ratio increase, the entire combustion process advances, and the ignition temperature, maximum peak temperature, and burnout temperature all show a decreasing trend. The kinetic equations of the combustion reaction process of mixed gas were calculated by Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) kinetic equations. The results show that the blending of TPW reduces the activation energy of the combustion reaction of the mixed fuel. When the TPW blending ratio is 80%, the activation energy values of the mixed fuel are the lowest at 111.32 kJ/mol and 104.87 kJ/mol. The abundant alkali metal ions and porous structure in TPW reduce the conversion rates of N and S elements in the fuel to NO and SO, thus reducing the pollutant emissions from the mixed fuel.
PubMed: 38930794
DOI: 10.3390/molecules29122728 -
Microorganisms Jun 2024Developing new anti-human immunodeficiency virus (HIV) drug candidates that target different sites in HIV-1 replication, with better resistance profiles and lower drug...
Developing new anti-human immunodeficiency virus (HIV) drug candidates that target different sites in HIV-1 replication, with better resistance profiles and lower drug toxicity, is essential to eradicating HIV. This study investigated the potential of fractionated crude extracts of as immunomodulatory or anti-HIV drug candidates. Solid-phase extraction (SPE) was used to fractionate PO4PR2 using three different columns: MAX (Mixed-mode, strong Anion-eXchange), MCX (Mixed-mode, strong Cation-eXchange), and HLB (Hydrophilic-Lipophilic Balance) with methanol gradient methods (5%, 45%, and 95%). An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to assess the cell viability and cytotoxicity of the fractionated crude extract PO4PR2 in the TZM-bl cell lines. This was followed by a luciferase-based antiviral assay to assess the antiviral activity of PO4PR2. A time of addition (TOA) assay was performed to ascertain the mechanism of inhibition employed by the fractionated crude extract of PO4PR2 in the HIV life cycle. The p24 titer was determined using an ELISA, while a luciferase-based antiviral assay was used to evaluate the HIV percentage inhibition for different HIV-1 replication cycles. The TOA assay was established using antiviral drugs that target different sites in the HIV replication cycle. These included maraviroc, azidothymidine, raltegravir, and amprenavir. The immunomodulatory effect of the fractionated crude extracts on CD4+ T cells was measured by a flow cytometric analysis, for which fluorochrome-labelled monoclonal antibodies were used as markers for activation (CD38 and HLA-DR) and exhaustion (PD-1). The MCX fraction demonstrated a more significant anti-HIV inhibition than that of the fractions generated in other columns, with an IC of 0.3619 µg/mL, an HIV inhibition of 77%, 5% HLB (IC: 0.7232 µg/mL; HIV inhibition of 64%), and 5% MAX (IC: 5.240 µg/mL; HIV inhibition of 67%). It was evident from the time of addition data that the crude extract and the 5% MCX fraction inhibited viral binding (68%), reverse transcription (75%), integration (98%), and proteolysis (77%). It was shown that (the MCX fraction) have a significant inhibitory effect on reverse transcription (75% HIV inhibition) and integration (100% HIV inhibition). The 5% MCX ( = 0.0062), 5% HLB ( = 0.0269), and 5% MAX ( = 0.0117) fractionated crude extracts had low levels of CD4+ T cell (CD38 + HLA-DR+) activation compared to those of the AZT treatment, while CD4+ T cell activation was insignificant. The 5% MAX and HLB fractions may possess immunomodulatory compounds with less anti-HIV-1 activity. could be a key source of innovative anti-HIV drugs with immunomodulatory characteristics.
PubMed: 38930532
DOI: 10.3390/microorganisms12061150 -
Materials (Basel, Switzerland) Jun 2024This work uses the direct current magnetron sputtering (DCMS) of equi-atomic (AlTiZrHfTa) and Si targets in dynamic sweep mode to deposit nano-layered (AlTiZrHfTa)N/SiN...
This work uses the direct current magnetron sputtering (DCMS) of equi-atomic (AlTiZrHfTa) and Si targets in dynamic sweep mode to deposit nano-layered (AlTiZrHfTa)N/SiN refractory high-entropy coatings (RHECs). Transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) are used to investigate the effect of Si addition on the oxidation behavior of the nano-layered coatings. The Si-free nitride coating exhibits FCC structure and columnar morphology, while the Si-doped nitride coatings present a FCC (AlTiZrHfTa)N/amorphous-SiN nano-layered architecture. The hardness decreases from 24.3 ± 1.0 GPa to 17.5 ± 1.0 GPa because of the nano-layered architecture, whilst Young's modulus reduces from 188.0 ± 1.0 GPa to roughly 162.4 ± 1.0 GPa. By increasing the thickness of the SiN nano-layer, k values decrease significantly from 3.36 × 10 g cm h to 6.06 × 10 g cm h. The activation energy increases from 90.8 kJ·mol for (AlTiZrHfTa)N nitride coating to 126.52 kJ·mol for the (AlTiZrHfTa)N/SiN nano-layered coating. The formation of a FCC (AlTiZrHfTa)-N/a-SiN nano-layered architecture results in the improvement of the resistance to oxidation at high temperature.
PubMed: 38930169
DOI: 10.3390/ma17122799 -
Life (Basel, Switzerland) Jun 2024Pomegranate fruit dry rot is caused by , also referred as . In order to decipher the induced responses of mature pomegranates inoculated with the pathogen, an RNA-seq...
Pomegranate fruit dry rot is caused by , also referred as . In order to decipher the induced responses of mature pomegranates inoculated with the pathogen, an RNA-seq analysis was employed. A high number of differentially expressed genes (DEGs) were observed through a three-time series inoculation period. The transcriptional reprogramming was time-dependent, whereas the majority of DEGs were suppressed and the expression patterns of specific genes may facilitate the pathogen colonization at 1 day after inoculation (dai). In contrast, at 2 dai and mainly thereafter at 3 dai, defense responses were partially triggered in delay. Particularly, DEGs were mainly upregulated at the latest time point. Among them, specific DEGs involved in cell wall modification and degradation processes, pathogen recognition and signaling transduction cascades, activation of specific defense and metabolite biosynthesis-related genes, as well in induction of particular families of transcriptional factors, may constitute crucial components of a defense recruiting strategy employed by pomegranate fruit upon challenge. Overall, our findings provide novel insights to the compatible interaction of pomegranates- and lay the foundations for establishing integrated pest management (IPM) strategies involving advanced approaches, such as gene editing or molecular breeding programs for disease resistance, according to European Union (EU) goals.
PubMed: 38929736
DOI: 10.3390/life14060752 -
Life (Basel, Switzerland) May 2024Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (, , , , and ) from the...
Recent studies have shown that seagrasses could possess potential applications in the treatment of inflammatory disorders. Five seagrass species (, , , , and ) from the Great Barrier Reef (QLD, Australia) were thus collected, and their preliminary antioxidant and anti-inflammatory activities were evaluated. From the acetone extracts of five seagrass species subjected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging antioxidant assay, the extract of had the highest activity (half minimal concentration of inhibition (IC) = 138 µg/mL), with the aerial parts (IC = 119 µg/mL) possessing significantly higher antioxidant activity than the roots (IC ≥ 500 µg/mL). A human peripheral blood mononuclear cells (PBMCs) assay with bacterial lipopolysaccharide (LPS) activation and LEGENDplex cytokine analysis showed that the aerial extract of significantly reduced the levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 by 29%, 74%, and 90%, respectively, relative to the LPS treatment group. The aerial extract was thus fractionated with methanol (MeOH) and hexane fraction, and purification of the MeOH fraction by HPLC led to the isolation of 4-hydroxybenzoic acid (), luteolin (), and apigenin () as its major constituents. These compounds have been previously shown to reduce levels of TNF-α, IL-1β, and IL-6 and represent some of the major bioactive components of aerial parts. This investigation represents the first study of the antioxidant and anti-inflammatory properties of and the first isolation of small molecules from this species. These results highlight the potential for using seagrasses in treating inflammation and the need for further investigation.
PubMed: 38929693
DOI: 10.3390/life14060710