Lambris

The aroma of coffee is a complex mixture of more than 1000 compounds. The volatile compounds in green and roasted coffee were analyzed to detect several features related to quality, roasting level, origins, and the presence of specific defects. With respect to specialty coffee, the flavor profile and peculiarities of the aforementioned characteristics are even more relevant knowing the expectations of consumers to find, in a cup of coffee, unicity bestowed by its origin and post-harvesting processes. In this work, which dealt with 46 lots of specialty Arabica coffee, we used HS-SPME/GC-MS to detect the volatile compounds in green coffees together with those in the same coffees roasted at three different levels to identify whether differences in headspace composition were ascribable to the origin, the post-harvesting processes, and the roasting profiles...

Within a short few years, the number of complement inhibitors that are either approved for therapeutic application or evaluated in late-stage clinical trials has expanded remarkably. The sudden emergence of this target area in the pipelines of many biotech start-ups and even large pharmaceutical companies appears even more surprising when considering that the involvement of the complement system in various clinical conditions had long been recognized. In many aspects, however, the complement system is far from being a traditional drug target, which may explain the delayed breakthrough of this therapeutic strategy...

The use of biomaterials in modern medicine has enabled advanced drug delivery strategies and led to reduced morbidity and mortality in a variety of interventions such as transplantation or hemodialysis. However, immune-mediated reactions still present a serious complication of these applications. One of the drivers of such reactions is the complement system, a central part of humoral innate immunity that acts as a first-in-line defense system in its own right but also coordinates other host defense responses...

PURPOSE: Total marrow (and lymphoid) irradiation (TMI-TMLI) is limited by the couch travel range of modern linacs, which forces the treatment delivery to be split into two plans with opposite orientations: a head-first supine upper-body plan, and a feet-first supine lower extremities plan. A specific field junction is thus needed to obtain adequate target coverage in the overlap region of the two plans. In this study, an automatic procedure was developed for field junction creation and lower extremities plan optimization...

In 2002, a new class of thymidylate synthase (TS) involved in the de novo synthesis of dTMP named Flavin-Dependent Thymidylate Synthase ( FDTS ) encoded by the thyX gene was discovered; FDTS is present only in 30% of prokaryote pathogens and not in human pathogens, which makes it an attractive target for the development of new antibacterial agents, especially against multi-resistant pathogens. We report herein the synthesis and structure-activity relationship of a novel series of hitherto unknown pyrido[1,2-e]purine-2,4(1H,3H) -dione analogues...

(1) Background: As biofortified fish meat is becoming increasingly available, the use of supplements within fish feed may impact consumers' perceptions and their willingness to pay (WTP) for the product. This study focused on evaluating the sensory liking of, and WTP for, fish produced with fortified feed while understanding the role played by the acquired information on fish fortification. (2) Methods: Hedonic ratings and WTP were measured in an experimental bid. The participants (n = 91) were asked to rate pleasantness and WTP during two different rounds: (i) appearance-information-tasting and (ii) appearance-tasting-information...

With the addition of the compstatin-based complement C3 inhibitor pegcetacoplan, another class of complement targeted therapeutics have recently been approved. Moreover, compstatin derivatives with enhanced pharmacodynamic and pharmacokinetic profiles are in clinical development (e.g., Cp40/AMY-101). Despite this progress, the target binding and inhibitory modes of the compstatin family remain incompletely described. Here, we present the crystal structure of Cp40 complexed with its target C3b at 2.0-Å resolution...

In both mice and humans, complement and Th17 cells have been implicated in periodontitis, an oral microbiota-driven inflammatory disease associated with systemic disorders. A recent clinical trial showed that a complement C3 inhibitor (AMY-101) causes sustainable resolution of periodontal inflammation, the main effector of tissue destruction in this oral disease. Although both complement and Th17 are required for periodontitis, it is uncertain how these immune components cooperate in disease development. In this study, we dissected the complement-Th17 relationship in the setting of ligature-induced periodontitis (LIP), a model that previously established that microbial dysbiosis drives Th17 cell expansion and periodontal bone loss...

Complement C3 activation contributes to COVID-19 pathology, and C3 targeting has emerged as a promising therapeutic strategy. We provide interim data from ITHACA, the first randomized trial evaluating a C3 inhibitor, AMY-101, in severe COVID-19 (PaO2/FiO2 ≤ 300 mmHg). Patients received AMY-101 ( n = 16) or placebo ( n = 15) in addition to standard of care. AMY-101 was safe and well tolerated. Compared to placebo (8 of 15, 53.3%), a higher, albeit nonsignificant, proportion of AMY-101-treated patients (13 of 16, 81...

No abstract text is available yet for this article.

Patients in the intensive care unit (ICU) often straddle the divide between life and death. Understanding the complex underlying pathomechanisms relevant to such situations may help intensivists select broadly acting treatment options that can improve the outcome for these patients. As one of the most important defense mechanisms of the innate immune system, the complement system plays a crucial role in a diverse spectrum of diseases that can necessitate ICU admission. Among others, myocardial infarction, acute lung injury/acute respiratory distress syndrome (ARDS), organ failure, and sepsis are characterized by an inadequate complement response, which can potentially be addressed via promising intervention options...

No abstract text is available yet for this article.

During the COVID-19 pandemic, much of the media focus has been on adaptive immunity, particularly antibody levels and memory T cells. However, immunologists have been striving to decipher how SARS-CoV-2 infection impacts our first line of defence, namely the innate immune system. In early 2022, Program staff from the NIAID at the NIH organized a workshop focusing on the innate immune response to SARS-CoV-2 infection and during COVID-19, which was chaired by Ralph Baric, Jenny Ting and John Lambris. Following the meeting, Nature Reviews Immunology invited some of the organizers and speakers to share their thoughts on the key discussion points...

The eye presents a unique opportunity for complement component 3 (C3) therapeutics. Drugs can be delivered directly to specific parts of the eye, and growing evidence has established a pivotal role for C3 in age-related macular degeneration (AMD). Emerging data show that C3 may be important to the pathophysiology of other eye diseases as well. This article will discuss the location of C3 expression in the eye as well as the preclinical and clinical data regarding C3's functions in AMD. We will provide a comprehensive review of developing C3 inhibitors for the eye, including the Phase 2 and 3 data for the C3 inhibitor pegcetacoplan as a treatment for the geographic atrophy of AMD...

This topical review focuses on the applications of artificial intelligence (AI) tools to stereotactic body radiation therapy (SBRT). The high dose per fraction and the limited number of fractions in SBRT require stricter accuracy than standard radiation therapy. The intent of this review is to describe the development and evaluate the possible benefit of AI tools integration into the radiation oncology workflow for SBRT automation. The selected papers were subdivided into four sections, representative of the whole radiotherapy process: 'AI in SBRT target and organs at risk contouring', 'AI in SBRT planning', 'AI during the SBRT delivery', and 'AI for outcome prediction after SBRT'...

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo ...

As the most abundant component of the complement system, C3 and its proteolytic derivatives serve essential roles in the function of all three complement pathways. Central to this is a network of protein-protein interactions made possible by the sequential proteolysis and far-reaching structural changes that accompany C3 activation. Beginning with the crystal structures of C3, C3b, and C3c nearly twenty years ago, the physical transformations underlying C3 function that had long been suspected were finally revealed...

The clinical manifestations of envenomation by Bothrops species are complex and characterized by prominent local effects that can progress to tissue loss, physical disability, or amputation. Systemic signs can also occur, such as hemorrhage, coagulopathy, shock, and acute kidney failure. The rapid development of local clinical manifestations is accompanied by the presence of mediators of the inflammatory process originating from tissues damaged by the bothropic venom. Considering the important role that the complement system plays in the inflammatory response, in this study, we analyzed the action of Bothrops jararaca snake venom on the complement system and cell surface receptors involved in innate immunity using an ex vivo human whole blood model...

Periodontitis is an inflammatory disease caused by biofilm accumulation and dysbiosis in subgingival areas surrounding the teeth. If not properly treated, this oral disease may result in tooth loss and consequently poor esthetics, deteriorated masticatory function and compromised quality of life. Epidemiological and clinical intervention studies indicate that periodontitis can potentially aggravate systemic diseases, such as, cardiovascular disease, type 2 diabetes mellitus, rheumatoid arthritis, and Alzheimer disease...

The complex molecular and cellular biological systems that maintain host homeostasis undergo continuous crosstalk. Complement, a component of innate immunity, is one such system. Initially regarded as a system to protect the host from infection, complement has more recently been shown to have numerous other functions, including involvement in embryonic development, tissue modeling, and repair. Furthermore, the complement system plays a major role in the pathophysiology of many diseases. Through interactions with other plasma cascades, including hemostasis, complement activation leads to the broad host-protective response known as thromboinflammation...