Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, Systemic Immune Inflammation Index and Efficacy of Remote Ischemic Conditioning in Acute Ischemic Stroke: A Post Hoc Exploratory Analysis of the RICAMIS Study.

Background: We conducted a post-hoc analysis of the RICAMIS trial to investigate the effect of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) on the efficacy of remote ischemic conditioning treatment.

Methods: In this post-hoc analysis, NLR, PLR, and SII were measured before randomization. Patients were divided into two groups based on their cut-off values: high vs low NLR, high vs low PLR, and high vs low SII groups.

Multidirectional characterization of cellular composition and spatial architecture in human multiple primary lung cancers.

Multiple primary lung cancers (MPLCs) pose diagnostic and therapeutic challenges in clinic. Here, we orchestrated the cellular and spatial architecture of MPLCs by combining single-cell RNA-sequencing and spatial transcriptomics. Notably, we identified a previously undescribed sub-population of epithelial cells termed as CLDN2 alveolar type II (AT2) which was specifically enriched in MPLCs.

GPR35 antagonist CID-2745687 attenuates anchorage-independent cell growth by inhibiting YAP/TAZ activity in colorectal cancer cells.

GPR35, a member of the orphan G-protein-coupled receptor, was recently implicated in colorectal cancer (CRC). However, whether targeting GPR35 by antagonists can inhibit its pro-cancer role has yet to be answered. We applied antagonist CID-2745687 (CID) in established GPR35 overexpressing and knock-down CRC cell lines to understand its anti-cell proliferation property and the underlying mechanism.

Aminosalicylates target GPR35, partly contributing to the prevention of DSS-induced colitis.

GPR35, a class A G-protein-coupled receptor, is considered an orphan receptor; the endogenous ligand and precise physiological function of GPR35 remain obscure. GPR35 is expressed relatively highly in the gastrointestinal tract and immune cells. It plays a role in colorectal diseases like inflammatory bowel diseases (IBDs) and colon cancer.

The roles of E3 ubiquitin ligases in cancer progression and targeted therapy.

Ubiquitination is one of the most important post-translational modifications which plays a significant role in conserving the homeostasis of cellular proteins. In the ubiquitination process, ubiquitin is conjugated to target protein substrates for degradation, translocation or activation, dysregulation of which is linked to several diseases including various types of cancers. E3 ubiquitin ligases are regarded as the most influential ubiquitin enzyme owing to their ability to select, bind and recruit target substrates for ubiquitination.

Norcantharidin overcomes vemurafenib resistance in melanoma by inhibiting pentose phosphate pathway and lipogenesis downregulating the mTOR pathway.

Melanoma is the most aggressive type of skin cancer with a high incidence and low survival rate. More than half of melanomas present the activating BRAF mutations, along which V600E mutant represents 70%-90%. Vemurafenib (Vem) is an FDA-approved small-molecule kinase inhibitor that selectively targets activated BRAF V600E and inhibits its activity.

PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1α.

PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC.

Midkine noncanonically suppresses AMPK activation through disrupting the LKB1-STRAD-Mo25 complex.

Midkine (MDK), a secreted growth factor, regulates signal transduction and cancer progression by interacting with receptors, and it can be internalized into the cytoplasm by endocytosis. However, its intracellular function and signaling regulation remain unclear. Here, we show that intracellular MDK interacts with LKB1 and STRAD to disrupt the LKB1-STRAD-Mo25 complex.

USP22 regulates lipidome accumulation by stabilizing PPARγ in hepatocellular carcinoma.

Elevated de novo lipogenesis is considered to be a crucial factor in hepatocellular carcinoma (HCC) development. Herein, we identify ubiquitin-specific protease 22 (USP22) as a key regulator for de novo fatty acid synthesis, which directly interacts with deubiquitinates and stabilizes peroxisome proliferator-activated receptor gamma (PPARγ) through K48-linked deubiquitination, and in turn, this stabilization increases acetyl-CoA carboxylase (ACC) and ATP citrate lyase (ACLY) expressions. In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments.

Silibinin relieves UVB-induced apoptosis of human skin cells by inhibiting the YAP-p73 pathway.

Excessive exposure to UVB induces skin diseases. Silibinin, a flavonolignan used for treating liver diseases, is found to be effective against UVB-caused skin epidermal and dermal cell damage. In this study we investigated the molecular mechanisms underlying.

Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite-Protein Interaction Network.

Metabolite-protein interactions (MPIs) play key roles in cancer metabolism. However, our current knowledge about MPIs in cancers remains limited due to the complexity of cancer cells. Herein, the authors construct an integrative MPI network and propose a MPI network based hepatocellular carcinoma (HCC) subtyping and mechanism exploration workflow.

YB1 regulates miR-205/200b-ZEB1 axis by inhibiting microRNA maturation in hepatocellular carcinoma.

Background: Y-box binding protein 1 (YB1 or YBX1) plays a critical role in tumorigenesis and cancer progression. However, whether YB1 affects malignant transformation by modulating non-coding RNAs remains largely unknown. This study aimed to investigate the relationship between YB1 and microRNAs and reveal the underlying mechanism by which YB1 impacts on tumor malignancy via miRNAs-mediated regulatory network.

AQP3-mediated H O uptake inhibits LUAD autophagy by inactivating PTEN.

It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In the current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H O ) and increase intracellular ROS levels.

Silibinin treatment protects human skin cells from UVB injury through upregulation of estrogen receptors.

Ultraviolet B (UVB) from the sunlight is a major environmental cause for human skin damages, inducing cell death, inflammation, senescence and even carcinogenesis. The natural flavonoid silibinin, clinically used as liver protectant, has protective effects against UVB-caused skin injury in vivo and in vitro. Silibinin is often classified as a phytoestrogen, because it modulates the activation of estrogen receptors (ERs).

F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.

E3 ubiquitin ligases play a critical role in cellular mechanisms and cancer progression. F-box protein is the core component of the SKP1-cullin 1-F-box (SCF)-type E3 ubiquitin ligase and directly binds to substrates by various specific domains. According to the specific domains, F-box proteins are further classified into three sub-families: 1) F-box with leucine rich amino acid repeats (FBXL); 2) F-box with WD 40 amino acid repeats (FBXW); 3) F-box only with uncharacterized domains (FBXO).

Activated toll-like receptor 4 is involved in oridonin-induced phagocytosis via promotion of migration and autophagy-lysosome pathway in RAW264.7 macrophages.

In our previous study, we demonstrated that oridonin enhances phagocytosis of apoptotic bodies by macrophage-like cells by inducing autophagy. However, the direct sensor of autophagy and the key event controlling phagocytosis remains unknown. Herein, we showed that Toll-like receptor 4 (TLR4), known to mediate immune responses, was activated by oridonin.

Persistent IKKα phosphorylation induced apoptosis in UVB and Poly I:C co-treated HaCaT cells plausibly through pro-apoptotic p73 and abrogation of IκBα.

Toll-like receptor 3 (TLR3), a member of pattern recognition receptors, is reported to initiate skin inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. Recently, we have discovered the NF-κB pathway activated by TLR3 is involved in apoptosis of UVB-Poly I:C-treated HaCaT cells. The real culprit for apoptosis has not been precisely identified since the system of NF-κB pathway is complex.

Sub-lethal ultraviolet B irradiation and Poly I:C treatment synergistically induced apoptosis of HaCaT cells through NF-κB pathway.

Ultraviolet B (UVB) irradiation exerts multiple effects on skin cells, inducing apoptosis, senescence and carcinogenesis. Toll-like receptor 3, a member of pattern recognition receptors, is reported to initiate inflammation by recognizing double-strand RNA (dsRNA) released from UVB-irradiated cells. It has not been studied, however, whether apoptosis induction in UVB irradiation is attributed to TLR3 activation.

Type I collagen promotes primary cilia growth through down-regulating HDAC6-mediated autophagy in confluent mouse embryo fibroblast 3T3-L1 cells.

Primary cilia are microtubule-based organelles that extend from nearly all vertebrate cells. Abnormal ciliogenesis and cilia length are suggested to be associated with hypertension and obesity as well as diseases such as Meckel-Gruber syndrome. Extracellular matrix (ECM), comprising cellular microenvironment, influences cell shape and proliferation.

Silibinin protects murine fibroblast L929 cells from UVB-induced apoptosis through the simultaneous inhibition of ATM-p53 pathway and autophagy.

Ultraviolet B (UVB) is a major cause of skin inflammation, leading to skin damage. Our previous in vivo study revealed that a natural flavonoid silibinin had marked anti-inflammatory effect on UVB-exposed murine skin. UVB exposure caused reduced autophagy in epidermis while it promoted autophagy in dermis.

Autophagy induced by silibinin protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis.

Ultraviolet B (UVB) in the sun light is a major cause of skin damage, which accompanies complex alterations in irradiated skin cells, including DNA lesions, oxidative stress, inflammation and caspase activation. The protection against UVB damage requires multiple interruptions such as repair of the DNA lesions, scavenging of the reactive oxygen species (ROS), repression of the inflammation and others. Silibinin is suggested as an anti-UVB reagent, but the underlying mechanisms have not been fully elucidated.

Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis.

Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation.