First-line systemic treatment for hepatocellular carcinoma: A systematic review and network meta-analysis.

The rapid development of novel therapeutic options for advanced hepatocellular carcinoma (aHCC) has generated some uncertainty about the rational choice of the systemic upfront treatment. So far, a variety of therapeutic strategies have been investigated, including the combination of immunecheckpoint inhibitors and anti-VEGF. To identify the treatment that should be preferred as front-line approach, we compared the efficacy and toxicity of a variety of therapeutic strategies. With this aim, we performed a systematic review and a meta-analysis of randomized clinical trials. OS, PFS, ORR and tolerability outcomes were considered, and for each outcome the treatment ranking was evaluated by the surface under the cumulative rankings (SUCRAs). Combination of Camrelizumab + Rivoceranib scored the best in OS, followed by Sintilimab + Bevacizumab, whereas Lenvatinib + Pembrolizumab showed higher probability to be the best treatment in PFS and Sintilimab + Bevacizumab performed best in ORR. Finally, Durvalumab is the most tolerated treatment.

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas.

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies.

Carbon Source Influences Antioxidant, Antiglycemic, and Antilipidemic Activities of Haloferax mediterranei Carotenoid Extracts.

Haloarchaeal carotenoids have attracted attention lately due to their potential antioxidant activity. This work studies the effect of different concentrations of carbon sources on cell growth and carotenoid production. Carotenoid extract composition was characterized by HPLC-MS. Antioxidant activity of carotenoid extracts obtained from cell cultures grown under different nutritional conditions was determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Ability Power (FRAP) and ß-carotene bleaching assays. The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed to determine if they could be used to reduce blood glucose and lipid absorption. The maximum production of carotenoids (92.2 µg/mL) was observed combining 12.5% inorganic salts and 2.5% of glucose/starch. Antioxidant, hypoglycemic, and antilipidemic studies showed that higher carbon availability in the culture media leads to changes in the extract composition, resulting in more active haloarchaeal carotenoid extracts. Carotenoid extracts obtained from high-carbon-availability cell cultures presented higher proportions of all-trans-bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas the presence 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased. The production of haloarchaeal carotenoids can be successfully optimized by changing nutritional conditions. Furthermore, carotenoid composition can be altered by modifying carbon source concentration. These natural compounds are very promising in food and nutraceutical industries.

Preparation, characterization, and bioactivity of Zingiber officinale Roscoe powder-based Pickering emulsions.

BACKGROUND: Biocompatible Pickering emulsions (PE) stabilized by tailor-made antioxidant-loaded particles have been known for some time now, but antioxidant-rich natural plant particle-based emulsions are much less well known. This study aimed to investigate the physico-chemical properties of commercial Zingiber officinale powders obtained from biological and conventional agricultural practice and ginger powder-based PE. RESULTS: The physico-chemical and biological properties of Zingiber officinale powders (GDPs) obtained from conventional (GDPC1 and GDPC2) and biological agricultural (GDPBIO) practices, and the properties of derived PE (PE_GDPs) were examined. All GDPs showed weak aggregation in aqueous media and a sufficiently hydrophobic surface to stabilize oil-in-water (O/W) PE against coalescence for at least 1 month. Zingiber officinale powders (2% w/w) derived from biological agricultural practices (GDPBIO) demonstrated the best emulsifying properties. The Zingiber officinale powders and PE_GDPs were also characterized by their phytochemical profiles. All the investigated samples exhibited ferric reducing ability power greater than the positive control, butylated hydroxytoluene (BHT), with values ranging from 91.21 to 102.63 µmol L-1 Fe (II) g-1 for GDPC2 and 05PE_GDPC1 (O/W=1:1), respectively. In ß-carotene bleaching test the following trend GDPC1 > GDPBIO > GDPC2 was observed. A 05PE_GDPBIO sample with the oil volume fraction equal to 50% was stable to oxidation and exhibited a promising α-amylase inhibitory activity. CONCLUSION: The results suggest that ginger powder should be used as a starting point to design biocompatible PEs for different applications in the functional food, nutraceutical, and pharmaceutical industries. In fact, powder and based PE are characterized by a promising antioxidant activity, carbohydrate hydrolyzing enzyme and lipase inhibitory properties. Further in vivo studies are necessary to confirm these findings. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Chemical Compositions and Antioxidant Activities of Essential Oils, and Their Combinations, Obtained from Flavedo By-Product of Seven Cultivars of Sicilian Citrus aurantium L.

In this work, seven Citrus aurantium essential oils (EOs) derived from flavedo of cultivars 'Canaliculata', 'Consolei', 'Crispifolia', 'Fasciata', 'Foetifera', 'Listata', and 'Bizzaria' were investigated. EOs were also combined in 1:1 (v/v) ratio to identify possible synergism or antagonism of actions. GC-MS analysis was done to investigate Eos' phytochemical profiles. The antioxidant activity was studied by using a multi-target approach based on FRAP, DPPH, ABTS, and ß-carotene bleaching tests. A great difference was observed in EOs' phytochemical profiles. d-limonene (33.35-89.17%) was the main monoterpene hydrocarbon, and α-Pinene, ß-myrcene, and ß-linalool were identified in almost all samples. Among EOs, only C3 showed high quantitative and qualitative variability in its chemical composition. The chemical diversity of EOs was also demonstrated by PCA and HCA statistical analysis. Samples C2, C4, C5, C6, and C7 were statistically similar to each other, while C1 and C3 were characterized as having a different amount of other compounds and oxygenated monoterpenes, respectively, with respect to the other EOs mentioned. The global antioxidant score (GAS) revealed that among the tested EOs, C. aurantium 'Fasciata' EO had the highest antioxidant potential, with a GAS value of -0.47, whereas among combinations, the EO obtained by mixing 'Canaliculata' + 'Bizzaria' was the most active. Comparison by theoretical and real data on inhibitory concentration (IC50) and FRAP values did not reveal any significant effect of synergism or antagonism of actions to be valid in all biological applied tests. These findings, considered together, represent an important starting point to understand which compounds are responsible for the activities and their future possible industrial application.