The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients.

Background: The application of chimeric antigen receptor (CAR)-T cells in solid tumors is hindered due to the lack of specific tumor antigen and limited clinical efficacy. Our aim is to develop and validate novel CAR-T cell therapy against metastatic colorectal cancer (CRC).

Methods: By analyzing the expression of B7-H3 in CRC tissue and cell lines using immunohistochemistry (IHC) and flow cytometry, respectively, we identified B7-H3 as a potential target in CRC.

The expression of PRMT5 is associated with postoperative chemotherapeutic outcome in colon cancer.

Background: Postoperative chemotherapy is an essential treatment in locally advanced colon cancer, however, effective biomarkers for predicting patients who will benefit from this therapy are lacking. This study aims to explore the clinical value of protein arginine methyltransferase 5 (PRMT5) in guiding adjuvant chemotherapy in patients with colon cancer.

Methods: PRMT5 expression was determined via immunohistochemistry (IHC) in tumor and paratumor samples from 199 colon cancer patients who underwent radical surgery.

Proteasome inhibition induces DNA methylation alteration by attenuating the synthesis of DNA methyltransferase 1 and 3B in colorectal cancer.

Proteasome is an essential organelle responsible for maintaining cellular protein homeostasis, but its relationship with DNA methylation remains unknown. In this study, we assessed DNA methylation of colorectal cancer (CRC) cells following treatment with proteasome inhibitors, and investigated the underlying mechanism of DNA methylation changes and the biological effects on CRC cells. We established that inhibition of proteasome leads to significant alterations in DNA methylation profile in CRC by suppressing the synthesis of DNA methyltransferases (DNMTs).

Tryptophan extends the life of cytochrome P450.

Powerfully oxidizing enzymes need protective mechanisms to prevent self-destruction. The flavocytochrome P450 BM3 from (P450) is a self-sufficient monooxygenase that hydroxylates fatty acid substrates using O and NADPH as co-substrates. Hydroxylation of long-chain fatty acids (≥C) is well coupled to O and NADPH consumption, but shorter chains (≤C) are more poorly coupled.

Tryptophan-96 in cytochrome P450 BM3 plays a key role in enzyme survival.

Flavocytochrome P450 from Bacillus megaterium (P450 ) is a natural fusion protein containing reductase and heme domains. In the presence of NADPH and dioxygen the enzyme catalyses the hydroxylation of long-chain fatty acids. Analysis of the P450 structure reveals chains of closely spaced tryptophan and tyrosine residues that might serve as pathways for high-potential oxidizing equivalents to escape from the heme active site when substrate oxidation is not possible.

Surface cysteines could protect the SARS-CoV-2 main protease from oxidative damage.

The SARS-CoV-2 main protease (M) is responsible for cleaving twelve nonstructural proteins from the viral polyprotein. M, a cysteine protease, is characterized by a large number of noncatalytic cysteine (Cys) residues, none involved in disulfide bonds. In the absence of a tertiary-structure stabilizing role for these residues, a possible alternative is that they are involved in redox processes.

Prevalence and spectrum of germline cancer susceptibility gene variants and somatic second hits in colorectal cancer.

Colorectal cancer (CRC) is one of the most heritable cancers, and genetic factors play an important role in the increased CRC risk. However, the well-established CRC-risk genes were limited for explaining the increased risk of CRC individuals. Germline mutations in DNA damage repair (DDR) genes have also been reported to be implicated in CRC heritability.

The Significance of MET Expression and Strategies of Targeting MET Treatment in Advanced Gastric Cancer.

Background: Accurate assessment of predictive biomarker expression is critical in patient selection in clinical trials or clinical practice. However, changes in biomarker expression may occur after treatment. The aim of the present study was to evaluate the effects of chemotherapy on MET expression in gastric cancer (GC).

PD-1 restrains IL-17A production from γδ T cells to modulate acute radiation-induced lung injury.

Background: Combining radiotherapy (RT) with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown to enhance anti-tumor effects in the treatment of non-small cell lung carcinoma (NSCLC). Pulmonary toxicity is a major adverse effect of thoracic RT in NSCLC patients, whether it is administered alone or in combination with PD-1/PD-L1 inhibitors. This study aimed to evaluate the potential pulmonary toxicity of RT combined with concurrent PD-1 inhibitor and to clarify the underlying mechanisms.

Two Tryptophans Are Better Than One in Accelerating Electron Flow through a Protein.

We have constructed and structurally characterized a azurin mutant , where two adjacent tryptophan residues (W124 and W122, indole separation 3.6-4.1 Å) are inserted between the Cu center and a Re photosensitizer coordinated to the imidazole of H126 (Re(H126)(CO)(4,7-dimethyl-1,10-phenanthroline)).

A novel PADRE-Kv1.3 vaccine effectively induces therapeutic antibodies and ameliorates experimental autoimmune encephalomyelitis in rats.

Previous studies have confirmed that selective blockade of Kv1.3 channels could modulate the activities of pathogenic T cells and microglia/macrophages, which play key roles in experimental autoimmune encephalomyelitis (EAE). In this study, we designed an anti-Kv1.

Topiramate modulates post-infarction inflammation primarily by targeting monocytes or macrophages.

Aims: Monocytes/macrophages response plays a key role in post-infarction inflammation that contributes greatly to post-infarction ventricular remodelling and cardiac rupture. Therapeutic targeting of the GABAA receptor, which is enriched in monocytes/macrophages but not expressed in the myocardium, may be possible after myocardial infarction (MI).

Methods And Results: After MI was induced by ligation of the coronary artery, C57BL/6 mice were intraperitoneally administered with one specific agonist or antagonist of the GABAA receptor (topiramate or bicuculline), in the setting of presence or depletion of monocytes/macrophages.

Electron Tunneling through Pseudomonas aeruginosa Azurins on SAM Gold Electrodes.

Robust voltammetric responses were obtained for wild-type and Y72F/H83Q/Q107H/Y108F azurins adsorbed on CH(3)(CH(2))(n)SH:HO(CH(2))(m)SH (n=m=4,6,8,11; n=13,15 m=11) self-assembled monolayer (SAM) gold electrodes in acidic solution (pH 4.6) at high ionic strengths. Electron-transfer (ET) rates do not vary substantially with ionic strength, suggesting that the SAM methyl headgroup binds to azurin by hydrophobic interactions.