Conflict of interest: JDL is the founder of Amyndas Pharmaceuticals, which develops complement inhibitors for therapeutic purposes; he has a broad portfolio of patents describing the use of complement inhibitors for therapeutic purposes (www.lambris.com/ patents), some of which are developed by Amyndas (US patents 8946145/9371365, 9630992) and Apellis (US patents 6319897, 7989589, 7888323). JDL is also the inventor of the compstatin technology licensed to Apellis Pharmaceuticals (i.e., 4(1MeW)7W/ POT-4/APL-1 and PEGylated derivatives such as pegcetacoplan and APL-9).

Emerging data indicate that complement and neutrophils are involved in the maladaptive host immune response that fuels hyper-inflammation and thrombotic microangiopathy increasing the mortality rate in coronavirus disease 2019 (COVID-19). Here, we investigated the interaction between complement and the platelet/neutrophil extracellular traps (NETs)/thrombin axis, using COVID-19 clinical samples, cell-based inhibition studies and NETs/human aortic endothelial cell (HAEC) co-cultures. Increased plasma levels of NETs, TF activity and sC5b-9 were detected in patients. Neutrophils yielded high tissue factor (TF) expression and released NETs carrying functionally active TF. Confirming our ex vivo findings, treatment of control neutrophils with COVID-19 platelet-rich plasma generated TF-bearing NETs that induced thrombotic activity of HAEC. Thrombin or NETosis inhibition or C5aR1 blockade attenuated platelet-mediated NET-driven thrombogenicity. Serum isolated from COVID-19 patients induces complement activation in vitro, which is consistent with high complement activity in clinical samples. Complement inhibition at the level of C3 with compstatin Cp40 disrupted TF expression in neutrophils. In conclusion, we provide a mechanistic basis that reveals the pivotal role of complement and NETs in COVID-19 immmunothrombosis. This study supports emerging strategies against SARS-CoV-2 infection that exploit complement therapeutics or NETosis inhibition.

An emerging outbreak of monkeypox infection is quickly spreading worldwide, being currently reported in more than 30 countries, with slightly less than 1000 cases. In the present preliminary report, we collected and synthesized early data concerning epidemiological trends and clinical features of the ongoing outbreak and we compared them with those of previous outbreaks. Data were pooled from six clusters in Italy, Australia, the Czech Republic, Portugal, and the United Kingdom, totaling 124 cases (for 35 of which it was possible to retrieve detailed information). The ongoing epidemic differs from previous outbreaks in terms of age (54.29% of individuals in their thirties), sex/gender (most cases being males), risk factors, and transmission route, with sexual transmission being highly likely. Also, the clinical presentation is atypical and unusual, being characterized by anogenital lesions and rashes that relatively spare the face and extremities. The most prevalent sign/symptom reported was fever (in 54.29% of cases) followed by inguinal lymphadenopathy (45.71%) and exanthema (40.00%). Asthenia, fatigue, and headache were described in 22.86% and 25.71% of the subjects, respectively. Myalgia was present in 17.14% of the cases. Both genital and anal lesions (ulcers and vesicles) were reported in 31.43% of the cases. Finally, cervical lymphadenopathy was described in 11.43% of the sample, while the least commonly reported symptoms were diarrhea and axillary lymphadenopathy (5.71% of the case series for both symptoms). Some preliminary risk factors can be identified (being a young male, having sex with other men, engaging in risky behaviors and activities, including condomless sex, human immunodeficiency virus positivity (54.29% of the sample analyzed), and a story of previous sexually transmitted infections, including syphilis). On the other hand, being fully virally suppressed and undetectable may protect against a more severe infectious course. However, further research in the field is urgently needed.

CD4 þ CD25 þ FOXP3 þ T regulatory cells (T regs ) prevent autoimmunity by restricting overexuberant immune responses, but the same subpopulation can incur detrimental effects on antitumor responses. In both cases, the suppressor potential of T regs appears to be strongly influenced by their compartmentalization. In myelodysplastic syndromes (MDS), immune deregulation and autoimmunity in the early stages might lead to ineffective hematopoiesis and bone marrow (BM) failure, whereas late-stage disease is characterized by the immune escape of the malignant clone. We show that these two stages of MDS are associated with differential T reg activity. Specifically, we found that in early stage MDS, compared with normal hematopoiesis and late stage MDS, T regs are dysfunctional and their BM homing through the CXCL12/CXCR4 axis is seriously impaired as a result of CXCR4 downregulation. Conversely, in late stage MDS, T regs are systemically and locally expanded and retain their function and migratory capacity. Moreover, T reg levels follow the disease course and are significantly reduced in treatment responding patients. Our findings indicate T reg involvement in the pathophysiology of MDS; defective suppressor function and BM trafficking of T regs may be important in the autoimmune process of early MDS, but increased T reg activity could favor leukemic clone progression in late stage disease.

The increasing incidence of drug- resistant pathogens raises an urgent need to identify and isolate new bioactive compounds from medicinal plants using standardized modern analytical procedures. Medicinal plant-derived compounds could provide novel straightforward approaches against pathogenic bacteria. This review explores the antimicrobial activity of plant-derived components, their possible mechanisms of action, as well as their chemical potential. The focus is put on the current challenges and future perspectives surrounding medicinal plants antimicrobial activity. There are some inherent challenges regarding medicinal plant extracts and their antimicrobial efficacy. Appropriate and optimized extraction methodology plant species dependent leads to upgraded and selective extracted compounds. Antimicrobial susceptibility tests for the determination of the antimicrobial activity of plant extracts may show variations in obtained results. Moreover, there are several difficulties and problems that need to be overcome for the development of new antimicrobials from plant extracts, while efforts have been made to enhance the antimicrobial activity of chemical compounds. Research on the mechanisms of action, interplay with other substances, and the pharmacokinetic and/or pharmacodynamic profile of the medicinal plant extracts should be given high priority to characterize them as potential antimicrobial agents.

No abstract

Since ancient times, the quality of nourishment is a milestone for the maintenance of health and as it is stated ‘prevention is better than cure’, amongst the so-called ‘healthy’ diets Mediterranean diet (MD) claims the lion’s share. It stands in good stead because of a variety of valuable macro- and micronutrients. So, adherence to a MD is associated with the reduction of inflammation and non-communicable (NCD) OR chronic diseases. Numerous studies try to scrutinize the role of MD components as regards reducing inflammation, lowering rate, and mortality for disorders and illnesses, and preventing NCD. MD regime of the inhabitants of the Mediterranean basin includes a variety of ethnic nutritional habits and regulates an array of effects and epigenetic changes that affect human wellbeing. The research is still ongoing and endeavors to elucidate every aspect of this issue. This review focuses on the impact of MD on inflammation highlights positive results regarding NCD and indicates the need for more high-quality experiments and trials in order to overcome any discrepancies.

Continuous infusion of 2% propofol at large doses for the sedation of rabbits undergoing prolonged mechanical ventilation induced fatal multiorgan dysfunction syndrome similar to the propofol infusion syndrome seen in humans. Our novel findings including lung, liver, gallbladder, and urinary bladder injury were also noted. The role of propofol's lipid vehicle in the manifestation of the syndrome was minor. Sevoflurane proved to be a safe alternative medication for prolonged sedation.