Targeting intracellular cancer proteins with tumor-microenvironment-responsive bispecific nanobody-PROTACs for enhanced therapeutic efficacy.

Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity.

Development of ZmT-PEG hydrogels through Michael addition reaction and protein self-assembly for 3D cell culture.

Bioactive protein-derived hydrogels are highly attractive three-dimensional (3D) platforms for cell culture. However, most protein and polypeptide hydrogels are extracted from animal tissues or chemically synthesized, with many drawbacks. Herein, we fabricated an optically transparent ZmT-PEG hydrogel a facile one-pot strategy.

Split-Cas9-based targeted gene editing and nanobody-mediated proteolysis-targeting chimeras optogenetically coordinated regulation of Survivin to control the fate of cancer cells.

Background: Precise regulation of partial critical proteins in cancer cells, such as anti-apoptotic proteins, is one of the crucial strategies for treating cancer and discovering related molecular mechanisms. Still, it is also challenging in actual research and practice. The widely used CRISPR/Cas9-based gene editing technology and proteolysis-targeting chimeras (PROTACs) have played an essential role in regulating gene expression and protein function in cells.

A nanobody-based molecular toolkit for ubiquitin-proteasome system explores the main role of survivin subcellular localization.

Targeted protein degradation is a powerful tool for determining the function of specific proteins nowadays. Survivin is the smallest member of the inhibitor of the apoptosis protein (IAP) family. It exists in the cytoplasm and nucleus of cells, but the exact function of survivin in different subcellular locations retained unclear updates due to the lack of effective and simple technical means.

Multistage targeting and dual inhibiting strategies based on bioengineered tumor matrix microenvironment-mediated protein nanocages for enhancing cancer biotherapy.

Regulation of the apoptotic pathway plays a critical role in inducing tumor cell death and circumventing drug resistance. Survivin protein is the strongest inhibitor of apoptosis found so far. It is highly expressed in several cancers and is a promising target for cancer therapy.

The Establishment of Quantitatively Regulating Expression Cassette with sgRNA Targeting to Elucidate the Synergistic Pathway of Survivin with P-Glycoprotein in Cancer Multi-Drug Resistance.

Quantitative analysis and regulating gene expression in cancer cells is an innovative method to study key genes in tumors, which conduces to analyze the biological function of the specific gene. In this study, we found the expression levels of Survivin protein () and P-glycoprotein () in MCF-7/doxorubicin (DOX) cells (drug-resistant cells) were significantly higher than MCF-7 cells (wild-type cells). In order to explore the specific functions of gene in multi-drug resistance (MDR), a CRISPR/Cas9-mediated knocking-in tetracycline (Tet)-off regulatory system cell line was established, which enabled us to regulate the expression levels of Survivin quantitatively (clone 8 named MCF-7/Survivin was selected for further studies).

Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment.

Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death.

The methyl jasmonate-responsive transcription factor SmMYB1 promotes phenolic acid biosynthesis in Salvia miltiorrhiza.

Water-soluble phenolic acids are major bioactive compounds in the medicinal plant species Salvia miltiorrhiza. Phenolic acid biosynthesis is induced by methyl jasmonate (MeJA) in this important Chinese herb. Here, we investigated the mechanism underlying this induction by analyzing a transcriptome library of S.

Improved phenolic acid content and bioactivities of Salvia miltiorrhiza hairy roots by genetic manipulation of RAS and CYP98A14.

Phenolic acids from Salvia miltiorrhiza have been widely used in nutritious, health-promoting products with an increasing demand. In the current study, two biosynthetic genes RAS (rosmarinic acid synthase) and CYP98A14 (a cytochrome P450-dependent monooxygenase) were successfully introduced into S. miltiorrhiza hairy roots.

ABA-responsive transcription factor bZIP1 is involved in modulating biosynthesis of phenolic acids and tanshinones in Salvia miltiorrhiza.

Phenolic acids and tanshinones are major bioactive ingredients in Salvia miltiorrhiza, which possess pharmacological activities with great market demand. However, transcriptional regulation of phenolic acid and tanshinone biosynthesis remains poorly understood. Here, a basic leucine zipper transcription factor (TF) named SmbZIP1 was screened from the abscisic acid (ABA)-induced transcriptome library.

SmMYB2 promotes salvianolic acid biosynthesis in the medicinal herb Salvia miltiorrhiza.

MYB transcription factors play vital roles in plant growth and metabolism. The phytohormone methyl jasmonate (MeJA) promotes phenolic acid accumulation in the medicinal herb Salvia miltiorrhiza, but the regulatory mechanism is poorly understood. Here, we identified the MeJA-responsive R2R3-MYB transcription factor gene SmMYB2 from a transcriptome library produced from MeJA-treated S.

Tanshinone and salvianolic acid biosynthesis are regulated by in hairy roots.

Bunge is an herb rich in bioactive tanshinone and salvianolic acid compounds. It is primarily used as an effective medicine for treating cardiovascular and cerebrovascular diseases. Liposoluble tanshinones and water-soluble phenolic acids are a series of terpenoids and phenolic compounds, respectively.

Tanshinone production could be increased by the expression of SmWRKY2 in Salvia miltiorrhiza hairy roots.

Tanshinones are the main bioactive diterpenes in Salvia miltiorrhiza Bunge, are widely used for treating cardiovascular and cerebrovascular diseases. However, the biosynthetic mechanisms of these compounds have not yet been fully explained. In this study, a transcription factor named SmWRKY2 was isolated and functionally characterized.

Bioactivities, biosynthesis and biotechnological production of phenolic acids in Salvia miltiorrhiza.

Salvia miltiorrhiza (Danshen in Chinese), is a well-known traditional Chinese medicinal plant, which is used as not only human medicine but also health-promotion food. Danshen has been extensively used for the treatment of various cardiovascular and cerebrovascular diseases. As a major group of bioactive constituents from S.