FEBS Open Bio最新文献

Proper glycemic control is crucial for patient management in critical care, including perioperative care, and can influence patient prognosis. Blood glucose concentration determines insulin secretion and sensitivity and affects the intricate balance between the glucose metabolism. Human and other animal studies have demonstrated that perioperative drugs, including volatile anesthetics and intravenous anesthetics, affect glucose-stimulated insulin secretion (GSIS). Dexmedetomidine (DEX) decreases insulin release and affects glucose metabolism; however, the specific mechanism underlying this phenomenon remains largely unknown. Thus, we investigated the effect and mechanism of DEX on insulin secretion using mouse and rat pancreatic β-cell-derived MIN6 and INS-1 cell lines and primary pancreatic β-cells/islets extracted from mice. The amount of insulin secreted into the culture medium was determined using an enzyme-linked immunosorbent assay. Cell viability, cytotoxicity, and electrophysiological effects were investigated. Clinically relevant doses of DEX suppressed GSIS in MIN6 cells, INS-1 cells, and pancreatic β-cells/islets. Furthermore, DEX suppressed insulin secretion facilitated by insulinotropic factors. There was no significant difference in oxygen consumption rate, intracellular ATP levels, or caspase-3/7 activity. Electrophysiological evaluation using the patch-clamp method showed that DEX did not affect ATP-sensitive potassium (K_ATP) channels, voltage-dependent potassium channels, or voltage-gated calcium channels. We demonstrated that clinically relevant doses of DEX significantly suppressed GSIS. These findings suggest that DEX inhibits a signaling pathway via α2-adrenoceptor or insulin vesicle exocytosis, resulting in GSIS suppression. Our results support the hypothesis that DEX suppresses insulin secretion and reveal some underlying mechanisms.

Frailty, a reversible clinical geriatric syndrome, impairs the ability to maintain homeostasis, leading to severe consequences such as hospitalization and death. Cognitive frailty, characterized by the co-occurrence of physical frailty and cognitive impairment, has garnered increasing attention in recent years. Preclinical models, especially rodent studies, are essential for understanding frailty and developing interventions to mitigate associated conditions. Traditionally, animal studies have focused solely on physical frailty. We have pioneered the inclusion of cognitive parameters by developing a novel physical-cognitive frailty score (FS) in animal research, in order to assess the effectiveness of anti-aging interventions. Here, we provide a detailed example of the FS calculation at the group level, which can serve as a guide for other studies. This dual-focus approach also helps in understanding how physical frailty and cognitive impairment interact to exacerbate adverse health outcomes and provides an opportunity to evaluate potential interventions that target both physical and cognitive dimensions of frailty more reliably.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a challenge for clinical treatment and combining antibiotics with other agents might be a promising strategy to overcome this challenge. This study explored the synergistic antibacterial activity of baicalin (traditional Chinese medicine extract) and the narrow-spectrum beta-lactam antibiotic oxacillin sodium, both of which are poorly active against MRSA in vitro. The combination of baicalin and oxacillin sodium showed a synergistic effect with a fractional inhibitory concentration index of 0.5. Mechanistically, the supplementation of baicalin increased the permeability of bacterial cell walls and cell membranes, enhancing oxacillin sodium entry and bactericidal action. The combination of baicalin and oxacillin sodium also significantly inhibited MRSA USA300 biofilm formation by further reducing polysaccharide intercellular adhesion production. Therefore, the combination of baicalin and oxacillin sodium offers a new therapeutic option for addressing clinical MRSA resistance. Further studies, including clinical trials, will be required to validate the observed in vitro results.

Oral squamous cell carcinoma (OSCC) is the one of the most common types of malignant tumor found in the head and neck area. Replication factor C subunit 4 (RFC4), an oncogene active in various human cancers, has been rarely studied in OSCC. In the present study, bioinformatics analysis identified RFC4 as a potential key target in OSCC progression. Additional experiments showed that RFC4 expression was significantly higher in OSCC tumor tissues than in normal tissues. Knockdown of RFC4 led to G2/M phase cell cycle arrest and inhibited the proliferation of OSCC cells both in vitro and in vivo. High RFC4 expression in OSCC tumors was linked to increased levels of MET, along with reduced levels of CD274 and CD160. Overall, the present study reveals that RFC4 may play a pivotal role in OSCC tumorigenesis and could serve as a potential predictive marker for the efficacy of immunotherapy.

Pathogenic Leptospira is the etiological cause of the zoonotic life-threatening infection called leptospirosis. The disease is spread worldwide with higher risk in tropical regions. Although leptospirosis represents a burden to the health of humans and animals, the pathogenic mechanisms of Leptospira infection are yet to be clarified. Leptospirosis infection is multifactorial, involving functionally redundant proteins with the capability to invade, disseminate, and escape the host's immune response. In this work, we describe a putative lipoprotein encoded by the gene LIC_13355, genome annotated as hypothetical of unknown function. The coding sequence is conserved among pathogenic Leptospira spp. with high percentage of coverage and identity. The recombinant protein, rLIC_13355, was expressed in Escherichia coli host system in its insoluble form. The circular dichroism spectrum of the refolded protein showed it containing a mixture of secondary structures. rLIC_13355 interacts with extracellular matrix (ECM) component laminin and binds plasminogen (PLG), generating plasmin (PLA), thus possibly participating during the adhesion and dissemination processes. The rLIC_13355 has the ability to interact with Ea.hy926 and HMEC-1 endothelial cells either in monolayer or suspension. The binding of rLIC_13355 with monolayer cells is dose-dependent on protein concentration. Taken together, our data suggest that this is presumably an adhesion lipoprotein that may play diverse roles in host-Leptospira interactions by mediating the interaction with host components and with endothelial cell.

The condition of cellular senescence has specific features, including an altered lipid metabolism. Delta-9 desaturase (Δ9) catalyzes the conversion of saturated fatty acids, such as palmitic acid and stearic acid, into their monounsaturated forms, palmitoleic and oleic acid, respectively. Δ9 activity is important for most lipid functions, such as membrane fluidity, lipoprotein metabolism and energy storage. The present study aimed to investigate differences in the expression of Δ9 in senescence-induced pancreatic (MIA-PaCa-2 and PANC-1) and hepatic (Hepa-RG and HLF) cancer cell lines. Cellular senescence was induced by growing cells in the presence of the chemotherapic drug doxorubicin. Senescence status was determined by the senescence-associated beta-galactosidase activity assay kit combined with the p21 and senescence associated secretory phenotype protein assay. Δ9 was downregulated in all senescence-induced cell lines compared to control cells, in both the lipidomic analysis and when measuring protein levels via western blotting. Hence, our findings demonstrate that the study of membrane lipid composition and the expression levels of Δ9 could potentially form the basis for future applications investigating the state of cellular senescence.

Several studies have suggested a potential antitumor effect of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD). To further understand the mechanism of action of this compound, we investigated its effect on the phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. We show that DMDD application significantly inhibited the proliferation of breast cancer cell lines MDA-MB-231 and ER-α positive MCF-7. Furthermore, DMDD application resulted in increased intracellular reactive oxygen species (ROS) levels, apoptosis and autophagy, whereas it downregulated the expression of PI3K, Akt and mTOR mRNA and proteins, and increased the expression of LC3II/I and p62 proteins. In a mouse breast cancer xenograft model, DMDD inhibited tumor growth. Expression analyses suggest that ROS levels were higher in DMDD treated tumor tissues, whereas immunohistochemical analyses suggest that apoptotic cells were more prevalent in the DMDD treated group compared to the control group. Taken together, our results suggest that the molecular mechanism of action of DMDD may involve the enhancement of breast cancer autophagy through the PI3K/Akt/mTOR signaling pathway by mediating ROS expression.

Retraction: R. Su, W. Su, and Q. Jiao, "NGF Protects Neuroblastoma Cells Against β-Amyloid-Induced Apoptosis via the Nrf2/HO-1 pathway," FEBS Open Bio 9, no. 12 (2019): 2063-2071, https://doi.org/10.1002/2211-5463.12742. The above article, published online on 01 November 2019, in Wiley Online Library (wileyonlinelibrary.com), and its correction (https://doi.org/10.1002/2211-5463.12782) has been retracted by agreement between the journal Editor-in-Chief, Miguel A. De la Rosa; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image duplications between this (Figure 2A, 3A, 5A and 6E) and other articles that were previously published or published in the same or following year. Given the extent of the identified issues, the editors have lost confidence in the data presented and consider the conclusions of this manuscript substantially compromised.

Retraction: Y. Xu, Y. Gao, Z. Huang, Y. Zheng, W. Teng, D. Zheng, and X. Zheng, "LKB1 Suppresses Androgen Synthesis in a Mouse Model of Hyperandrogenism via IGF-1 Signaling," FEBS Open Bio 9, no. 10 (2019): 1817-1825, https://doi.org/10.1002/2211-5463.12723. The above article, published online on 12 September 2019, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Miguel A. De la Rosa; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image duplications between this (Figure 1C, 1H) and other articles that were previously published or published in the same or following year. Given the extent of the identified issues, the editors have lost confidence in the data presented and consider the conclusions of this manuscript substantially compromised.

Retraction: T. Wang, L. Ma, W. Li, L. Ding, and H. Gao, "MicroRNA-498 Reduces the Proliferation and Invasion of Colorectal Cancer Cells via Targeting Bcl-2," FEBS Open Bio 10, no. 1 (2020): 168-175, https://doi.org/10.1002/2211-5463.12767. The above article, published online on 17 December 2019, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Miguel A. De la Rosa; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image duplications between this (Figure 3A and B, 5E and F) and other articles that were previously published or published in the same or following year. Given the extent of the identified issues, the editors have lost confidence in the data presented and consider the conclusions of this manuscript substantially compromised.