In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic ...activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice. In this review, the chemistry of ADC linker conjugation together with strategies adopted to improve antibody tolerability (by reducing antigenicity) are examined, with particular attention to ADCs approved by the regulatory agencies (the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA)) for treating cancer patients. Recent developments in engineering Immunoglobulin (Ig) genes and antibody humanization have greatly reduced some of the problems of the first generation of ADCs, beset by problems, such as random coupling of the payload and immunogenicity of the antibody. ADC development and clinical use is a fast, evolving area, and will likely prove an important modality for the treatment of cancer in the near future.
COVID-19 is the global pandemic that affected our population in the past 2 years. Considerable research has been done to better understand the pathophysiology of this disease and to identify new ...therapeutic targets, especially for severe cases. Galectin-3 (Gal-3) is a receptor present at the surface of different cell types, namely epithelial and inflammatory cells, which has been described as a severity marker in COVID-19. The activation of Gal-3 through its binding protein (Gal-3BP) is directly linked to the production of pro-inflammatory cytokines that contribute for the cytokine storm (CS) observed in severe COVID-19 patients. Here, we show that D2, a recombinant fragment of the lectin-binding region of Gal-3BP was able to stimulate the expression of IL-6 in colon and lung epithelial cell lines in β-galactoside dependent manner. We further show that D2-induced IL-6 augmentation was reduced by the anti-Gal-3BP monoclonal antibody 1959. Our data confirm and extend prior findings of Gal-3BP mediated IL-6 induction, enlightening the potential of its antibody-mediated s blockage for the prevention and treatment of CS and severe disease in COVID-19 patients.
The decline of soil organic matter (SOM) and its associated fertility is one of the most important constraints to enhanced crop productivity in sub-Saharan Africa. Integrated soil fertility ...management recognizes the potential benefits of the combined use of organic residue and mineral fertilizer inputs for improved crop yield and SOM build up. However, these benefits may be controlled by residue quality. We examined the short- to long-term C and N dynamics following application of different quality residues with and without N fertilizer in a series of experiments comprising different timescales of measurement in a Kenyan Humic Nitisol. The combined results of these studies indicate that residue quality and fertilizer additions alter short-term C and N mineralization. Combining low quality residue and fertilizer inputs immobilized a greater amount of fertilizer-N than high quality residue. Under field conditions, this reduction in available N induced by the combination of low quality residue and fertilizer reduced environmental N losses and created a positive interactive effect on crop N uptake. While input management manipulated short-term nutrient dynamics, it did not influence long-term SOM stabilization. The input of residue, regardless of quality, contributed to long-term soil fertility improvement. In conclusion, organic residue quality can be manipulated to optimize short-term nutrient dynamics while still conferring the same benefits to long-term SOM contents.
As agricultural intensification affects global environmental change, a redesign of our food production systems towards practices that replace external inputs with inbuilt ecosystem services is ...needed. Specifically, human-induced changes to biogeochemical flows of nitrogen (N) cycling exceed the proposed planetary boundaries, highlighting a priority area for reducing nutrient inputs in agricultural production systems. A new understanding of nutrient interactions in the complete agroecosystem will allow us to better predict and mitigate the consequences of anthropogenic environmental changes compared with a reductionist approach. Here, we review for the first time system-level nutrient interactions, particularly N, in perennial horticulture using high-producing kiwifruit and apple crops grown in New Zealand as a basis to identify critical knowledge gaps and prioritize new research. The major points identified are (1) current nutrient guidelines are from the 1980s to the early 2000s and do not take into account substantial production changes since that time; (2) few studies construct complete nutrient budgets of all sources and losses; (3) nutrient loss estimates are generally low relative to those from other agricultural land uses; (4) there is a lack of studies which address nutrient interactions between above- and below-ground food webs in perennial horticultural crops; (5) there is contradictory literature where fertilizer has been found both to increase and to decrease plant chemical signaling and defense mechanisms. New tools are emerging to improve orchard nutrient management, including advances in fertilizer application techniques, new methods to monitor plant and soil nutrients, and utilizing genetic variability to breed cultivars with improved nutrient use efficiency. To reduce adverse nutrient effects on the environment, new research is needed, addressing the relationships between carbon and nutrients and nutrient demands in modern fruit cultivars and growing systems; the nutrient balance for perennial horticultural crops considering all inputs and outputs; and interactions of the above- and below-ground nutrient flows in orchard food webs.
Neuroblastoma is the most common extra-cranial solid tumor in infants and children, which accounts for approximately 15% of all cancer-related deaths in the pediatric population. New therapeutic ...modalities are urgently needed. Antibody-Drug Conjugates (ADC)s-based therapy has been proposed as potential strategy to treat this pediatric malignancy. LGALS3BP is a highly glycosylated protein involved in tumor growth and progression. Studies have shown that LGALS3BP is enriched in extracellular vesicles (EV)s derived by most neuroblastoma cells, where it plays a critical role in preparing a favorable tumor microenvironment (TME) through direct cross talk between cancer and stroma cells. Here, we describe the development of a non-internalizing LGALS3BP ADC, named 1959-sss/DM3, which selectively targets LGALS3BP expressing neuroblastoma. 1959-sss/DM3 mediated potent therapeutic activity in different types of neuroblastoma models. Notably, we found that treatments were well tolerated at efficacious doses that were fully curative. These results offer preclinical proof-of-concept for an ADC targeting exosomal LGALS3BP approach for neuroblastomas.
Background: An estimated 75% of women will have one episode of vulvovaginal candidiasis (VCC) during their lifetime, and 40–50% of these will experience further episodes. The high incidence of ...vulvovaginal candidiasis, combined with the problems of azole resistance and toxicity, highlights the necessity for new strategies for the treatment of this condition. In this context, natural compounds represent promising alternatives. Methods: We enrolled, between January 2020 and April 2021, forty women affected by uncomplicated vulvovaginal candidiasis. Women were divided into two groups. In the first group, we treated 20 women with clotrimazole daily administration for six days. In the second group, 20 women were treated with clotrimazole associated with Unilen® Microbio+, a new product containing Saccharomyces cerevisiae, melatonin, and GLA-14. Women underwent a check at days 15, 30, and 90. A clinical and cultural examination were performed to establish the effect of the treatments on vaginal flora. Results: In the group treated with Unilen® Microbio+, clinical and microbiological cure at 15 and 30 days was observed in 18 women (90%), compared with 16 women (80%) in the group treated only with clotrimazole. The efficacy of the association between clotrimazole and Unilen® Microbio+ in these uncomplicated forms was therefore not inferior to the azole treatment alone. Only four women (20%) in the Unilen® Microbio+ group presented symptomatic recurrences within the 3 months, compared with eight women (40%) in the clotrimazole-only group. Microscopic wet mount analysis at 1 and 3 months demonstrated a significant increase in lactobacillus count and a reduction in the polymorphonucleate cells in the Unilen® Microbio+ group. Conclusions: Unilen® Microbio+ supplementation was demonstrated to cure uncomplicated vulvovaginal candidiasis with clotrimazole, reducing recurrence and improving vaginal flora better than clotrimazole treatment alone.
La valutazione della rugosità superficiale del suolo è importante in agricoltura sotto molteplici aspetti: nello studio delle relazioni tra le rugosità della superficie e volume massimo di ...stoccaggio di acqua nelle depressioni della superficie per lo sviluppo di modelli idrologici da utilizzare nelle strategie di conservazione del suolo e dell'acqua; ogni qualvolta occorra definire lo stato di amminutamento delle zolle determinato dagli strumenti agricoli di lavorazione del suolo in relazione all’umidità e alle caratteristiche fisiche del suolo. Lo scopo di questo lavoro è stato quello di calibrare una nuova metodologia di misura della Rugosità Superficiale del Suolo (Random Roughness), basata sull’analisi di immagini stereoscopiche ricavate con Metodologia PAP (Pole Aerial Photography). La nuova metodologia si pone due obbiettivi innovativi fondamentali: misurare la Rugosità superficiale su ampie aree campionarie, al fine di una migliore rappresentazione delle superfici; ricavare i valori di rugosità con una tecnologia speditiva a basso costo.
Altered soil nutrient cycling under future climate scenarios may affect pasture production and fertilizer management. We conducted a controlled-environment study to test the hypothesis that long-term ...exposure of pasture to enriched carbon dioxide (CO
2
) would lower soil nutrient availability. Perennial ryegrass was grown for 9 weeks under ambient and enriched (ambient + 120 ppm) CO
2
concentrations in soil collected from an 11.5-year free air CO
2
enrichment experiment in a grazed pasture in New Zealand. Nitrogen (N) and phosphorus (P) fertilizers were applied in a full factorial design at rates of 0, 12.5, 25 or 50 kg N ha
−1
and 0, 17.5 or 35 kg P ha
−1
. Compared to ambient CO
2
, under enriched CO
2
without P fertilizer, total plant biomass did not respond to N fertilizer, and tissue N/P ratio was increased indicating that P was co-limiting. This limitation was alleviated with the lowest rate of P fertilizer (17.5 kg P ha
−1
). Plant biomass in both CO
2
treatments increased with increasing N fertilizer when sufficient P was available. Greater inputs of P fertilizer may be required to prevent yield suppression under enriched CO
2
and to stimulate any response to N.
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