Roles of TULA-family proteins in T cells and autoimmune diseases.

The T cell Ubiquitin Ligand (TULA) protein family contains two members, UBASH3A and UBASH3B, that display similarities in protein sequence and domain structure. Both TULA proteins act to repress T cell activation via a combination of overlapping and nonredundant functions. UBASH3B acts mainly as a phosphatase that suppresses proximal T cell receptor (TCR) signaling.

Targeted therapy of multiple myeloma by IL21-NKG2D CAR-T cells.

NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay.

Association between situs inversus and maternal SARS-CoV-2 infection at gestational age 4-6 weeks.

Background: A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus.

Methods: In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement.

CD39 tumor infiltrating T cells from colorectal cancers exhibit dysfunctional phenotype.

Recent studies revealed that CD39 was highly expressed in tumor-specific CD4 tumor infiltrating lymphocytes (TILs). However, the divergent function of CD39 T cells remains to be elucidated in colorectal cancer (CRC). In this study, T cells from CRC patients and tumor-bearing mice were isolated to evaluate the function of CD39 in T cells.

Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating β-Catenin signaling.

In the effort to identify deubiquitinating enzymes required for the growth of colorectal cancer (CRC) cells, we found that OTUB2 knockdown markedly inhibited the viability of these cancer cells in culture and in xenografted mice. It was also found that the level of OTUB2 was elevated in primary CRCs, and its high expression was a poor prognostic indicator for the patients. Interestingly, immunoprecipitation and LC-MS/MS analyses suggested that β-Catenin was an OTUB2-interacting protein, and there was a positive correlation between OTUB2 and β-Catenin expression in both CRC tissues and cell lines.

PYR-41, an inhibitor of ubiquitin-activating enzyme E1, attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous studies have shown that PYR-41 has effects on anti-inflammatory, but whether it has therapeutic effects on allergic dermatitis is unclear. The aim of this research was to explore the therapeutic effects of PYR-41 on atopic dermatitis.

Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis.

Background: Genetic compensation response (GCR) is a mechanism that maintains the robustness of functional genes, which has been recently identified. Whether GCR exists in tumors and its effects on tumor progression remains unknown.

Methods: Whole exome sequencing was performed to identify premature termination codon (PTC) gene mutations in colorectal cancer (CRC) tissues.

Targeting Adenylate Cyclase Family: New Concept of Targeted Cancer Therapy.

The adenylate cyclase (ADCY) superfamily is a group of glycoproteins regulating intracellular signaling. ADCYs act as key regulators in the cyclic adenosine monophosphate (cAMP) signaling pathway and are related to cell sensitivity to chemotherapy and ionizing radiation. Many members of the superfamily are detectable in most chemoresistance cases despite the complexity and unknownness of the specific mechanism underlying the role of ADCYs in the proliferation and invasion of cancer cells.

Histochemical Staining of Vasculogenic Mimicry.

Vasculogenic mimicry (VM) describes a new tumor microvascular paradigm of non-endothelial cells, where aggressive cancer cells independent of angiogenesis acquire the ability to fluid-conducting vessels. VM shows worse 5-year overall survival in cancer that suggesting that VM could be a promising surgical and effective adjuvant therapy strategy in prognostics of metastatic cancer patients. The current chapter is a comprehensive review on "Main Staining Methods and Protocols in Vasculogenic Mimicry.

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy.

With the advantages of tumor-targeting, pH-responsive drug releasing, and biocompatibility, ferritin nanocage emerges as a promising drug carrier. However, its wide applications were significantly hindered by the low loading efficiency of hydrophobic drugs. Herein, we redesigned the inner surface of ferritin drug carrier (ins-FDC) by fusing the C- terminus of human H ferritin (HFn) subunit with optimized hydrophobic peptides.

Topoisomerase 2 inhibitor etoposide promotes interleukin-10 production in LPS-induced macrophages via upregulating transcription factor Maf and activating PI3K/Akt pathway.

Topoisomerase (TOP) inhibitors were commonly used as chemotherapeutic agents in the treatment of cancers. In our present study, we found that etoposide (ETO), a topoisomerase 2 (TOP2) inhibitor, upregulated the production of Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-stimulated macrophages. Besides, other TOP2 inhibitors including doxorubicin hydrochloride (DOX) and teniposide (TEN) were also able to augment IL-10 production.

Qing-Fei-Pai-Du decoction and wogonoside exert anti-inflammatory action through down-regulating USP14 to promote the degradation of activating transcription factor 2.

COVID-19 is often characterized by dysregulated inflammatory and immune responses. It has been shown that the Traditional Chinese Medicine formulation Qing-Fei-Pai-Du decoction (QFPDD) is effective in the treatment of the disease, especially for patients in the early stage. Our network pharmacology analyses indicated that many inflammation and immune-related molecules were the targets of the active components of QFPDD, which propelled us to examine the effects of the decoction on inflammation.

Loss of BRMS2 induces cell growth inhibition and translation capacity reduction in colorectal cancer cells.

A variety of chemotherapeutic drugs targeting ribosome processing have been developed and applied to cancer treatment mainly based on the impaired ribosome biogenesis checkpoint (IRBC). The IMP U3 small nucleolar ribonucleoprotein 3 (IMP3, BRMS2) has been identified as a participant in pre-rRNA processing for nearly twenty years. However, the roles of BRMS2 in cancers still unknown.