Polyphenolic content, in vitro antioxidant activity and chemical composition of extract from Nephelium lappaceum L.(Mexican rambutan) husk

Objective: To determinate the recovery of total polyphenolic compounds content,in vitro antioxidant activity and HPLC/ESI/MS characterization of extract from Nephelium lappaceum L.(Mexican rambutan).Methods: The rambutan husk extract was obtained by aqueous extraction and a polyphenolic fraction was recovered using Amberlite XAD-16. The total polyphenolic compounds content was determined by the Folin Ciocalteu and butanol-HCI methods.In vitro antioxidant activity was performed using ABTS and ferric reducing antioxidant power methods.Results: Mexican rambutan husk showed a total polyphenolic content of 582 mg/g and an evident antioxidant activity by ABTS and ferric reducing antioxidant power analysis.The HPLC/ESI/MS assay allowed the identification of 13 compounds, most of which belong to ellagitannins. Geraniin, corilagin and ellagic acid were present in the sample;the mineral composition was also evaluated.Conclusions: Rambutan husk cultivated in Mexico is a promising source for the recovery of added value bioactive compounds with antioxidant activity, which have potential applications as bioactive antioxidant agents for the treatment of diseases.

Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α

Chinese hamster ovary(CHO)cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational modifications.However,toxic proteins and membrane proteins are often difficult-to-express in living cells.Alternatively,cell-free protein synthesis can be employed.This study explores innovative strategies for enhancing the production of challenging proteins through the modification of CHO cells by investigating both,cell-based and cell-free approaches.A major result in our study involves the integration of a mutant eIF2 translation initiation factor and T7 RNA polymerase into CHO cell lysates for cell-free protein synthesis.This resulted in elevated yields,while eliminating the necessity for exogenous additions during cell-free production,thereby substantially enhancing efficiency.Additionally,we explore the potential of the Rosa26 genomic site for the integration of T7 RNA polymerase and cell-based tetracycline-controlled protein expression.These findings provide promising advancements in bioproduction technologies,offering flexibility to switch between cell-free and cell-based protein production as needed.

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3

The TEA domain(TEAD)family proteins(TEAD1-4)are essential transcription factors that control cell differentiation and organ size in the Hippo pathway.Although the sequences and structures of TEAD family proteins are highly conserved,each TEAD isoform has unique physiological and pathological functions.Therefore,the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases.Here,we identified a novel TEAD 1/3 covalent inhibitor(DC-TEADin1072)with biochemical IC50 values of 0.61±0.02 and 0.58±0.12μmol/L against TEAD1 and TEAD3,respectively.Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DCTEAD3 in03 with the IC_(50) value of 0.16±0.03μmol/L,which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling(ABPP)assays.In cells,DC-TEAD3 in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD(1-4)reporter assays with the IC50 value of1.15μmol/L.When administered to zebrafish juveniles,experiments showed that DC-TEAD3 in03 reduced the growth rate of zebrafish caudal fins,indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages.

Nanocarrier drugs in the treatment of brain tumors

Nanoparticle-mediated targeted delivery of drugs might significantly reduce the dosage and optimize their release properties,increase specificity and bioavailability,improve shelf life,and reduce toxicity.Some nanodrugs are able to overcome the blood-brain barrier that is an obstacle to treatment of brain tumors.Vessels in tumors have abnormal architecture and are highly permeable;moreover,tumors also have poor lymphatic drainage,allowing for accumulation of macromolecules greater than approximately 40 kDa within the tumor microenvironment.Nanoparticles exploit this feature,known as the enhanced permeability and retention effect,to target solid tumors.Active targeting,i.e.surface modification of nanoparticles,is a way to decrease uptake in normal tissue and increase accumulation in a tumor,and it usually involves targeting surface membrane proteins that are upregulated in cancer cells.The targeting molecules are typically antibodies or their fragments;aptamers;oligopeptides or small molecules.There are currently several FDA-approved nanomedicines,but none approved for brain tumor therapy.This review,based both on the study of literature and on the authors own experimental work describes a comprehensive overview of preclinical and clinical research of nanodrugs in therapy of brain tumors.