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Aims: Current methods to induce tolerance following allotransplantation or in autoimmunity carry significant morbidity, and research is very active in investigating alternative methods which could minimize toxicity. Spheroids from adipose stem cells (SASCs) are increasingly gaining interest, they hold a great proliferative and differentiating potential. An immunomodulatory effect has not been investigated on SASCs yet. In this study, we analysed the immunomodulatory properties of SASCs and compared them to ADSCs., Main Methods: Adipose stem cells (SASCs and ADSCs) and peripheral blood mononuclear cells (PBMCs) were collected from healthy individuals. We analysed the cytokine production and proliferation of T cells co-cultured with adipose samples or conditioned medium., Key Findings: SASCs modulated cytokines production and proliferation of heterologous and autologous T cells. In the heterologous assays, we observed a reduction of IFNγ and IL-17 production and an increase of IL-9 in γδ T cells. The soluble factors present in SASCs sovranatants were also able to induce a slight reduction of IFNγ and an increase of IL-9, IL-10 and IL-17 while they could not modulate the proliferative ability of γδ T cells. In the autologous assays, we observed a reduction of the proliferative ability of T cells in co-culture at different ratios with SASCs. Analysis of the SASCs secretome showed an increased IL-5, IL-10, IL-4 and IL-13 production compared to the ADSCs one, demonstrating greater anti-inflammatory properties., Significance: Our preliminary results support the idea that SASCs exert more pronounced biological immune modulation compared to the classical adherent ADSCs, especially in heterologous experimental settings., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None reports was provided by none. None reports a relationship with none that includes: None has patent pending to none. None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: To study the relationship between respiratory/allergic disorders and chronic environmental tobacco smoke (ETS) exposure to husband or at workplace among non-smoking women of a general population in Italy., Methods: Analyses regard 2195 married or employed women. Information was collected through a self-administered questionnaire. ETS exposure was validated by salivary cotinine., Results: Exposure both to husband and at work resulted a significant risk factor for current dyspnoea (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.20-2.16), any shortness of breath at rest (OR 2.81, 95% CI 1.83-4.30), recent wheeze (OR 1.71, 95% CI 1.04-2.82), recent attacks of shortness of breath with wheeze (OR 1.85, 95% CI 1.05-3.26), asthma diagnosis/symptoms (OR 1.50, 95% CI 1.09-2.08), diagnosis of asthma or bronchitis/emphysema (obstructive lung diseases (OLD)) (OR 2.24, 95% CI 1.40-3.58), current cough/phlegm (OR 1.52, 95% CI 1.07-2.15), and rhino-conjunctivitis (OR 1.48, 95% CI 1.13-1.94). Exposure only at work yielded higher adjusted odds ratios for all health conditions, except for rhino-conjunctivitis. Overall, about 24% of shortness of breath at rest, 16% of dyspnoea, 17% of rhino-conjunctivitis, 12% of OLD, and 10% of asthma diagnosis/symptoms are attributable to the effect of exposures to both husband and at work. Twelve percent of shortness of breath at rest and 10% of rhino-conjunctivitis cases might be avoided by eliminating exposure only at work and only to husband, respectively., Conclusions: Lifetime ETS exposure, especially at work, is associated with respiratory symptoms/diseases, and it accounts for a sizeable proportion of such disorders. The combined effect of both exposures is higher than the separate effects.

A series of milrinone analogues, namely 6-substituted 3-acetyl-5-acylpyridin-2(1H)-ones 4a-c, e, f and 7-substituted or unsubstituted 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones 4g-j, in which the cyano group was replaced by the acetyl function, was prepared. In a preliminary pharmacological investigation on spontaneously beating atria from reserpine-treated guinea-pigs, all new compounds did not induce any inotropic effect equivalent or higher than that of the milrinone chosen as the reference compound. In order to rationalise how the structure modifications influence the activity and the selectivity of the title compounds, a computational study has been performed. The important role of the substituents in positions-3 and -6 on the pyridone nucleus has been highlighted.

A series of pyrazole analogues of bifonazole, an antifungal drug used in clinical practice, 2a-h and 4a-h were synthesized and tested in vitro against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, with no significant results. Imidazoles 2a-h were also tested in vivo for antiarrhythmic and antihypertensive activities; two of these compounds showed moderate activity against ventricular fibrillation caused by aconitine in rats. The above compounds were prepared by reaction of phenyl-[5 substituted 1-phenyl (or 1-methyl)-1H-pyrazol-4-yl]methanols with N,N'-carbonyldiimidazole (2a-h) or of the respective chloro derivatives with 1H-1,2,4-triazole (4a-h).

A series of angelicin heteroanalogues, in which the furan was replaced by thiophene or a 1-substituted pyrazole moiety, was synthesised in order to obtain potential therapeutic agents with antiproliferative and/or other biological activities. In general, the antiproliferative activity of the new thioangelicin, tested in different biological substrates, appeared to be higher than that of the angelicin, the natural parent compound, but lower than that of 8-MOP, the furocoumarin ordinarily used in PUVA therapy and photopheresis. Thioangelicin 6 induced strong inhibition of T2 bacteriophage infectivity and was able to significantly repress the DNA synthesis in Ehrlich ascites cells and the clonal growth in HeLa cells. The pyrazolocoumarins did not show any noticeable effect upon UVA irradiation in all the biological systems considered. All the new angelicin heteroanalogues appeared to be free of the known phototoxicity of furocoumarins on the skin. The pyrazolocoumarins have also been tested as anti-inflammatory, analgesic, antipyretic, local anaesthetic, anti-arrhythmic and platelet anti-aggregating agents by standard procedures. In this class of derivatives, 10a showed good anti-inflammatory and antipyretic properties, while 9a and 11a showed significant local anaesthetic activity.

The synthesis of 6-substituted 5-acyl-1,2-dihydro-2-oxo-3-pyridinecarbonitriles 1b,c, 1,2,5,6,7,8-hexahydro-2,5-dioxo-3-quinolinecarbonitriles 1d-g and esters of 5-cyano-1,6-dihydro-2-methyl-6-oxo-3-pyridinecarboxylic acid 2b-e is described. In the case of 1e and 1f, a careful elucidation of the reaction mechanism is discussed. As milrinone analogues, the above compounds were tested on contractile activity and frequency rate of spontaneously beating atria from reserpine-treated guinea pigs. The methyl and the benzyl esters 2b and 2e showed an appreciable positive inotropic activity when compared to milrinone. A fitting study with the DISCO (Distance Comparison) model has been carried out on 2e. This modeling approach allowed for the improvement of the pharmacophoric requirements for a better interaction with the cAMP-specific PDE (PDE III), thought to be the final biological target of these cardiotonic agents.