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Natural products possess pleiotropic cardiovascular protective effects owing to their anti-oxidation, anti-inflammation and anti-thrombotic properties. Kaempferol, (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one), is a kind of naturally occurring flavonoid existing in many common fruits and vegetables (e.g., onions, broccoli, strawberries and grapes) and particularly in traditional Chinese medicine as exemplified by Ginkgo biloba. Epidemiological, preclinical and clinical studies have revealed an inverse association between the consumption of kaempferol-containing foods and medicines and the risk of developing cardiovascular diseases. Numerous translational studies in experimental animal models and cultured cells have demonstrated a wide range of pharmacological activities of kaempferol. In this article, we reviewed the antioxidant, anti-inflammatory and cardio-protective activities of kaempferol and elucidated the potential molecular basis of the therapeutic capacity of kaempferol by focusing on its anti-atherosclerotic effects. Overall, the review presents the health benefits of kaempferol-containing plants and medicines and reflects on the potential of kaempferol as a possible drug candidate to prevent and treat atherosclerosis, the underlying pathology of most cardiovascular diseases.

Cannabinoids have emerged as promising neuroprotective agents due to their capability to activate specific targets, which are involved in the control of neuronal homeostasis and survival. Specifically, those ligands that selectively target and activate the CB2 receptor may be useful for their anti inflammatory and neuroprotective properties in various neurological disorders, with the advantage of being devoid of psychotropic effects associated with the activation of CB1 receptors. The aim of this work has been to investigate the neuroprotective properties of 7-(1,1-dimethylheptyl)-4,4-dimethyl-9- methoxychromeno[3,4-d]isoxazole (PM226), a compound derived from a series of chromeno-isoxazoles and −pyrazoles, which seems to have a promising profile related to the CB2 receptor. The compound binds selectively to this receptor with an affinity in the nanomolar range (Ki = 12.8 ± 2.4 nM). It has negli gible affinity for the CB1 receptor (Ki > 40000 nM) and no activity at the GPR55. PM226 was also evaluated in GTP S binding assays specific to the CB2 receptor showing agonist activity (EC50 = 38.67 ± 6.70 nM). In silico analysis of PM226 indicated that it has a good pharmacokinetic profile and a predicted abil ity to cross the blood-brain barrier. Next, PM226 was investigated in an in vitro model to explore its anti-inflammatory/neuroprotective properties. Conditioned media were collected from LPS-stimulated cultures of BV2 microglial cell line in the absence or presence of different doses of PM226, and then media were added to cultured M213-2O neuronal cells to record their influence on cell viability evaluated using MTT assays. As expected, cell viability was significantly reduced by the exposure to these conditioned media, while the addition of PM226 attenuated this reduction in a dose-dependent manner. This effect was reversed by co-incubating with the CB2 antagonist SR144528, thus confirming the involvement of CB2 receptors, whereas the addition of PM226 to neuronal cu, Ministerio de Economía, Comercio y Empresa, Centro de Investigación Biomédica en Red (CIBERNED), Comunidad de Madrid, Depto. de Bioquímica y Biología Molecular, Fac. de Medicina, TRUE, pub

Purpose: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. Materials and methods: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. Results: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1‑month COVID-19 mortality (OR = 0.302 [0.106–0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control

Foxtail millet (Setaria italica), which was domesticated from the wild species green foxtail (Setaria viridis), is a rich source of phytonutrients for humans. To evaluate how breeding changed the metabolome of foxtail millet grains, we generated and analyzed the datasets encompassing the genomes, transcriptomes, metabolomes, and anti-inflammatory indices from 398 foxtail millet accessions. We identified hundreds of common variants that influence numerous secondary metabolites. We observed tremendous differences in natural variations of the metabolites and their underlying genetic architectures between distinct sub-groups of foxtail millet. Furthermore, we found that the selection of the gene alleles associated with yellow grains led to altered profiles of metabolites such as carotenoids and endogenous phytohormones. Using CRISPR-mediated genome editing we validated the function of PHYTOENE SYNTHASE 1 (PSY1) gene in affecting millet grain color and quality. Interestingly, our in vitro cell inflammation assays showed that 83 metabolites in millet grains have anti-inflammatory effects. Taken together, our multi-omics study illustrates how the breeding history of foxtail millet has shaped its metabolite profile. The datasets we generated in this study also provide important resources for further understanding how millet grain quality is affected by different metabolites, laying the foundations for future millet genetic research and metabolome-assisted improvement.

Casein glycomacropeptide (CGMP) is a bioactive milk-derived peptide with potential anti-inflammatory effects. Animal studies suggest that CGMP may work by altering gut microbiota composition and enhancing butyrate production. Its effects on intestinal homeostasis, microbiota and metabolites in humans are unknown. The aim of the present study was to assess both the intestinal and systemic immunomodulatory effects of orally ingested CGMP. We hypothesised that a daily oral CGMP intake would reduce high-sensitive C-reactive protein in healthy adults. In a single-centre limited but randomised, double-blinded, reference-controlled study, we compared the effects of a four-week intervention of either 25 grams of oral powder-based chocolate-flavoured CGMP or a reference drink. We included twenty-four healthy adults who all completed the study. CGMP had no systemic or intestinal immunomodulatory effects compared with a reference drink, either with regard to high-sensitive C-reactive protein, or faecal calprotectin level, faecal microbiota composition or faecal short-chain fatty acid content. CGMP ingestion did not affect satiety or body weight, and it caused no severe adverse events. The palatability of CGMP was acceptable and adherence was high. CGMP did not induce or change gastrointestinal symptoms. In conclusion, we found no immunomodulatory effects of CGMP in healthy adults. In a minor group of healthy adults, oral ingestion of 25 grams of CGMP during four weeks was safe, well tolerated, had acceptable palatability, and was without any effects on body weight.

Purpose To evaluate the efficacy and safety of lung low-dose radiation therapy (LD-RT) for pneumonia in patients with coronavirus disease 2019 (COVID-19). Materials and methods Inclusion criteria comprised patients with COVID-19-related moderate-severe pneumonia warranting hospitalization with supplemental O-2 and not candidates for admission to the intensive care unit because of comorbidities or general status. All patients received single lung dose of 0.5 Gy. Respiratory and systemic inflammatory parameters were evaluated before irradiation, at 24 h and 1 week after LD-RT. Primary endpoint was increased in the ratio of arterial oxygen partial pressure (PaO2) or the pulse oximetry saturation (SpO(2)) to fractional inspired oxygen (FiO(2)) ratio of at least 20% at 24 h with respect to the preirradiation value. Results Between June and November 2020, 36 patients with COVID-19 pneumonia and a mean age of 84 years were enrolled. Seventeen were women and 19 were men and all of them had comorbidities. All patients had bilateral pulmonary infiltrates on chest X-ray. All patients received dexamethasone treatment. Mean SpO(2) pretreatment value was 94.28% and the SpO(2)/FiO(2) ratio varied from 255 mm Hg to 283 mm Hg at 24 h and to 381 mm Hg at 1 week, respectively. In those who survived (23/36, 64%), a significant improvement was observed in the percentage of lung involvement in the CT scan at 1 week after LD-RT. No adverse effects related to radiation treatment have been reported. Conclusions LD-RT appears to be a feasible and safe option in a population with COVID-19 bilateral interstitial pneumonia in the presence of significant comorbidities.

Portulaca oleracea L. (Purslane) has great potential as food and traditional drugs in several countries. The purpose of this study was to evaluate the anti-inflammatory effects of purslane extract on lipopolysaccharide (LPS)stimulated RAW 264.7 cells. Purslane extracts significantly reduced LPS-induced synthesis of NO in a dose-dependent manner, as well as the expression levels of iNOS and COX-2. The productions of TNF-alpha and IL-6 were also significantly reduced at the higher dose of 400 mu g/ml. Meanwhile, the expression levels of P65, p-P65, p-MEK and p-I kappa B-alpha were inhibited dose-dependently. The nuclear translocation of P65 was partially prevented by the extract, which explained the inhibition of NF-kappa B pathway. In addition, three reported flavonoids, named luteolin, kaempferol and quercitrin, were identified in the extract, which might be responsible for its anti-inflammatory effects. Above all, our research has partially proved that purslane could be considered as a natural anti-inflammatory agent in further applications.

Skoro 30 godina terapija zvučnim udarnim talasima (engl. Extracorporeal Shock Wave Therapy, ESWT) je u upotrebi u kliničkoj praksi kao efikasan tretman za razbijanje kamena u urinarnom traktu. Ova tehnologija je kasnije razvijena i kao efikasan neinvazivan tretman za različite indikacije u ortopediji i traumatologiji uključujući i komplikovane rane koje ne zarastaju. Udarni zvučni talasi su tranzijentni, kratkotrajni akustički pulsevi sa visokim pikom pritiska, koji se dostiže u veoma kratkom vremenu, mereno nanosekunadama (jedan bilioniti deo sekunde). Udarni zvučni talasi koji se koriste u medicini se generišu putem tri tipa generatora i fizičkih rešenja: elektrohidraulički, piezoelektrični i elektromagnetni čiji je krajnji cilj da prenese fizičku energiju do ciljnog tkiva. Odloženo zarastanje, ili rane koje ne zarastaju predstavljaju veliki teret za svakog pacijenta, značajno umanjujući njegov kvalitet života. Velika briga o pacijentu i rani je neophodna u ovim slučajevima i ovo je veliki problem za društvo u smislu smanjene produktivnosti ljudi kao i smislu velikih finansijskih izdataka za zdravstvo. Sa druge strane, teške povrede kao one koje se viđaju u oružanim sukobima i saobraćajnim nesrećama predstavljaju glavni uzrok smrti u mlađoj adultnoj populaciji. Tehnološki napredak, i napredak u dostupnim terapeuticima, koji dovodi do inicijalnog povećanja preživljavanja pacijenata nije praćen razvojem lekova koji su usmereni protiv moguće prateće sistemske inflamacije, koja često progresira do sindroma sistemskog inflamatornog odgovora i sindroma propadanja organskih sistema koji mogu dovesti i do smrtnog ishoda. Zbog svega prethodno pomenutog, finansijski pristupačni, neinvazivni i efikasni tretmani su neophodni da bi se postiglo ubrzavanje i potpuno zarastanje problematičnih rana kao i redukovala cena lečenja. Zbog toga je neophodno utvrditi potencijalnu primenljivost ESWT u relevantnim animalnim modelima i kod pacijenata, i ispitati i razjasniti biološke mehani, For almost 30 years, extracorporeal shock wave therapy (ESWT) has been implemented clinically and has proven to be an effective treatment for urinary stones. This technology has also emerged as an efficacious non - invasive treatment modality for several orthopedic and traumatic indications including problematic soft tissue wounds. Shock waves are produced as transient short - term acoustic pulses with high peak pressure and a very rapid rise to peak pressure on the order of magnitude of nanoseconds (one billionth of a second). Sho ck waves for use in medicine can be generated using different physical principles - electro - hydraulic, piezoelectric and electromagnetic – with the goal of delivering physical energy to target tissue of interest in order to create a desired biological effect. Delayed/non - healing or chronic wounds constitute a burden for each patient affected, significantly impairing quality of life (QOL). Intensive multi - modality wound care is required, and this places an enormous burden on society in terms of lost producti vity and healthcare costs. Severe traumatic wounds seen in civilian and combat related injuries are a major cause of death amongst the younger population. Technological and therapeutic advances that lead to improved initial survival of patients with life - t hreatening injuries were unparalleled in therapeutics development to fight concomitant systemic inflammation that accompanies these injuries. This systemic inflammatory response to wounding often leads to development of a well - known syndrome - systemic inf lammatory response syndrome (SIRS) - and can progress to multiple organ dysfunction syndrome (MODS) and death. Because of all of the aforementioned, cost - effective, non - invasive, and efficacious treatments are imperative to achieve both (accelerated and co mplete) healing of problematic wounds and reduce treatment - related costs to the human and the healthcare system. Therefore, the potential of therapeutic shock wav

Background Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects. The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels an

Background Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects. The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels an

Background Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects. The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels an

Background Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects. The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels an

Background Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX®. The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects. The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels an

Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB. Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data. Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate. Conclusions: The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seem