Biochemistry and Cell Biology最新文献

The paper aimed to reveal the impacts and the possible mechanism of action of lectin mannose-binding 2 protein (LMAN2) in HER2-positive breast cancer (BC). The expression, prognostic potential of LMAN2, and the correlation between LMAN2 and HEAT repeat containing 3 (HEATR3) in BC were analyzed in TCGA database. Intact, Mentha, and BioGrid databases predicted LMAN2-HEATR3 interactions. Reverse transcription-quantitative PCR and Western blot examined LMAN2 expression. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, wound healing, and transwell assays, respectively, detected the aggressive cellular biological behaviors including proliferation, migration, and invasion. Western blot analyzed the expression of matrix metalloproteinases, HEATR3, and protein kinase B (Akt)/extracellular signal-regulated kinase (ERK)/nuclear factor-kappaB (NF-κB) signaling-related proteins. Co-immunoprecipitation assay was used to prove the relationship of LMAN2 with HEATR3. Enzyme-linked immunosorbent assay detected inflammatory cytokine levels. LMAN2 was overexpressed in HER2-positive BC tissues and cells and indicated unfavorable prognosis of BC patients. LMAN2 knockdown suppressed HER2-positive BC cell proliferation, migration, and invasion. LMAN2 interacted with and had a positive correlation with HEATR3. HEATR3 up-regulation reversed the repressive role of LMAN2 interference in the progression of HER2-positive BC, Akt/ERK/NF-κB signaling, and inflammatory response. Altogether, LMAN2 silencing might exert anti-tumor and anti-inflammatory properties and inactivate Akt/ERK/NF-κB signaling in HER2-positive BC via binding to HEATR3.

Mitotic bookmarking, the retention of regulatory proteins and lncRNAs on chromatin during mitosis, epigenetically sustains competency for phenotype-specific gene expression in progeny cells. Gene expression is predominantly suppressed during mitosis. Bookmarking provides the guidance for the resumption of gene expression in progeny cells that is obligatory for physiological control of lineage commitment, specialized cell structure and phenotypic function. While regulatory continuity is supported by the persistence of genome-associated regulatory complexes, altered bookmarking mediates plasticity for responsiveness to physiological cues. Bookmarking fidelity ensures genome integrity and controls expression of tumor suppressors and proto-oncogenes. Cancer-compromised aberrations in bookmarking results in transcriptional dysregulation and the initiation of tumor-associated processes.

Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein, involved in a wide range of bioactivities, including immunomodulatory and antiviral activities. Lf in human milk and bovine Lf added to infant formula may provide some protection against viral infections. However, functions of Lfs from different sources may differ due to varying manufacturing processes and posttranslational modifications. Here, effects of Lfs (11 commercial bovine milk Lfs, 2 recombinant Lfs, and native human/bovine milk Lf) on cytokine responses to virus infection were examined by infecting human intestinal epithelial cells (Caco-2 cells) with rotavirus (naked) or normal human bronchial epithelial cells (BEAS-2B cells) with respiratory syncytial virus (RSV, enveloped) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein 1. Effects of Lf on viral infection were evaluated by quantitative real-time polymerase chain reaction analysis of transcripts of cytokines/chemokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IFN-β, and CXCL10). Our results show that viral infection changes transcription of these cytokines and that Lfs significantly and variously influence immune responses to rotavirus, RSV, and SARS-CoV-2 in vitro. Thus, Lf may provide protection against virus infection by down-regulating pro-inflammatory cytokine/chemokine responses. Recombinant bovine and human Lf show similar effects as bovine milk Lfs suggesting that different posttranslational modifications do not affect the antiviral activity on cytokine response.

Galectins consist of a highly conserved carbohydrate recognition domain that involves in functional cellular activities including cell growth, cell proliferation and adhesion, signal transduction, and others. It has been reported that galectins play varying roles in distinct tissue types and have been implicated in different diseases, including cancer. Each of these proteins have its specific function and studies on the role of galectins in colorectal cancer mostly focusing on galectin-1, -3, -4, and -9. Thus, this review highlights the role of certain galectins in colorectal cancer, as well as their involvement in clinical trials.

Lactoferrin (Lf), we have previously shown, has therapeutic potential in the field of skeletal regenerative medicine demonstrating its potent stimulating effects on bone growth. Recently, we have identified bovine lactoferrin (bLf) as a factor that also enhances antibiotic killing of Staphylococcus aureus (S. aureus). Biofilms are associated with around 65% of all infections and 80% of chronic infections. One feature of biofilm infection is tolerance to antibiotics due to the survival of a subpopulation of biofilm bacteria, where laboratory tests on planktonic cells indicate susceptibility. Tolerance is seen in bone infections of osteomyelitis and prosthetic joints, where methicillin-susceptible S. aureus (MSSA) strains predominate, but where treatments with the frontline penicillinase-resistant antibiotic cefazolin (CEF) can be ineffective. In vitro-grown biofilms of MSSA are 1000-fold more tolerant to CEF but can be eradicated by CEF at 10x minimal inhibitory concentration in the presence of bLf. Bone infection can impede blood circulation within the bone, leading to bone death. Lf as a potent stimulator of bone growth adds to its appeal as a treatment for bone infections.

Surface receptors in Gram-negative bacteria that bind and extract iron from the host glycoproteins transferrin (Tf) or lactoferrin (Lf) was discovered 35 years ago in pathogenic Neisseria species and subsequently was discovered in other pathogens of humans and food production animals. These bacterial species reside exclusively on the mucosal surfaces of the respiratory or genitourinary tract of their mammalian host and rely on their host specific Tf and Lf receptors to acquire iron for survival. Since the specificity of the bacterial Tf receptors was shown to be due to selective pressures on the host Tf, their presence in bacteria that reside in both mammals and birds indicates that they arose over 320 million years ago. Once Lf arose in mammals due to a gene duplication event, Lf receptors subsequently arose from Tf receptors. The focus on pathogens for discovery of these receptors has led to a limited understanding of how prevalent the Tf and Lf receptors are in commensal species and raises the question whether they are present in additional bacterial lineages. Since the Lf receptor provides a secondary iron acquisition system plus can provide protection from cationic peptides its presence varies in bacterial lineages.

Epicardial adipose tissue (EAT) is a rich source of EAT-derived stromal cells (EATDS), which possess regenerative potential. CRSP2, HSP27, IL8, HSP90, and Cofilin 1 were detected in the secretome of left ventricular stromal cells under ischemia challenge. However, the association of these genes in the EAT and EATDS remain understudied. We aim to assess the status of cofilin 1, CRSP2, HSP27, IL8, and HSP90 in the EAT of myocardial infarction (MI) and coronary artery bypass graft (CABG) swine models and in vitro stimulated ischemic EATDS. Expression status of these proteins in EAT were assessed by immunostaining, and in EATDS using qRT-PCR, immunostaining, and Western blot. EATDS phenotyping was performed using sc-RNAseq analysis. Cofilin 1 was increased while the other four genes were decreased in the CABG. IL8 and HSP90 were increased, while CRSP2, HSP27, and cofilin 1 were decreased in the MI group. Similar trend was displayed in the expression of these genes in EATDS. Additionally, EATDS displayed versatile phenotypes at single cell resolution based on the differential expression of various gene signatures. The findings revealed novel insights into EAT/EATDS biology and further understanding regarding the EATDS sub-phenotypes would open novel avenues in translational cardiology.

The 67th Canadian Society for Molecular Biosciences (CSMB) Annual Conference took place in Winnipeg, Manitoba, from 6 May to 8 May 2024, at the University of Manitoba, Winnipeg. The conference theme "Gene Regulation: From Cells to Systems" was selected to reflect the breadth and multidisciplinary nature of CSMB's membership and to facilitate interactions among scientists and researchers across different disciplines and with diverse research programs and approaches. This meeting attracted registered participants from provinces across Canada and the USA. The objective of this meeting was to promote the inclusive dissemination, conversation, and discussions of molecular biosciences research, in different areas of molecular biosciences covering a wide range of topics in basic science and health-related research subjects such as neuroscience, cancer biology, immunology, physiology, bacterial systems, RNA biology, protein homeostasis, cellular metabolism and cell death mechanisms, neurobiology and neurogenetics, epigenetics, chromatin biology, environmental influence, stem cell biology, and genome-wide studies. This meeting provided a discussion opportunity for molecular bioscience researchers to develop innovative and novel strategies and collaborations for biomedical and translational research.

Estrogen receptor alpha (ERα) is an established biomarker for breast tumors, the loss of which is associated with poor cancer progression. Over 70% of breast cancers express ERα and targeting this protein has helped stem the progress of breast cancer. Therefore, it is paradoxical that only a small fraction of patients with ovarian and uterine cancers, which express ERα, are insensitive to antiestrogenic therapies. We propose the hypothesis that ERα association with different cofactors dictates the susceptibility of these cancers to therapies. To support this hypothesis, we analyzed data from cBioportal patient samples and showed that a strong positive correlation exists between ERα and its cofactors GATA3 and FOXA1 in breast cancer, but not in ovarian and uterine cancers. We further show that ERα genomic localization differs in the three cancer types, using available ChIP-seq datasets. Together, our analyses suggest that both localization and the nature of co-factors might be relevant for driving ERα-dependent cancer progression in different cell environments. We further discuss potential mechanisms for these differences in this commentary.