Bismuth-based mesoporous nanoball carrying sorafenib for synergistic photothermal and molecularly-targeted therapy in an orthotopic hepatocellular carcinoma xenograft mouse model.

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release.

Sulfiredoxin-1 promotes the growth of hepatocellular carcinoma by inhibiting TFEB-mediated autophagy and lysosome biogenesis.

Advanced hepatocellular carcinoma (HCC) patients have poor prognosis. As an endogenous antioxidant enzyme involved in a variety of bioprocesses, sulfiredoxin-1 (SRXN1) plays an irreplaceable role in promoting the development of tumors. However, the role and working mechanism of SRXN1 in HCC remain unclear.

Multi-Omics profiling identifies aldehyde dehydrogenase 2 as a critical mediator in the crosstalk between Treg-mediated immunosuppression microenvironment and hepatocellular carcinoma.

Dysregulation of the aldehyde dehydrogenase (ALDH) family has been implicated in various pathological conditions, including cancer. However, a systematic evaluation of ALDH alterations and their therapeutic relevance in hepatocellular carcinoma (HCC) remains lacking. Herein, we found that 15 of 19 ALDHs were transcriptionally dysregulated in HCC tissues compared to normal liver tissues.

Repolarization of Immunosuppressive Macrophages by Targeting SLAMF7-Regulated CCL2 Signaling Sensitizes Hepatocellular Carcinoma to Immunotherapy.

Unlabelled: Immune checkpoint inhibitors have limited efficacy in hepatocellular carcinoma (HCC). Macrophages are the most abundant immune cells in HCC, suggesting that a better understanding of the intrinsic processes by which tumor cells regulate macrophages could help identify strategies to improve response to immunotherapy. As signaling lymphocytic activation molecule (SLAM) family members regulate various immune functions, we investigated the role of specific SLAM receptors in the immunobiology of HCC.

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants.

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3.

Gut-liver axis calibrates intestinal stem cell fitness.

The gut and liver are recognized to mutually communicate through the biliary tract, portal vein, and systemic circulation. However, it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy and transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, which restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/β-catenin signaling pathway.

Transferrin receptor 1 promotes hepatocellular carcinoma progression and metastasis by activating the mTOR signaling pathway.

Background: Aberrant iron metabolism is commonly observed in multiple tumor types, including hepatocellular carcinoma (HCC). However, as the key regulator of iron metabolism involved in iron absorption, the role of transferrin receptor (TFRC) in HCC remains elusive.

Methods: The mRNA and protein expression of TFRC were evaluated in paired HCC and adjacent non-tumor specimens.

Genome-wide enhancer identification by massively parallel reporter assay in Arabidopsis.

Enhancers are critical cis-regulatory elements controlling gene expression during cell development and differentiation. However, genome-wide enhancer characterization has been challenging due to the lack of a well-defined relationship between enhancers and genes. Function-based methods are the gold standard for determining the biological function of cis-regulatory elements; however, these methods have not been widely applied to plants.

Synergistic Photochemo Effects Based on Light-Activatable Dual Prodrug Nanoparticles for Effective Cancer Therapy.

Ferroptosis is identified as a novel type of cell death with distinct properties involved in physical conditions and various diseases, including cancers. It is considered that ferroptosis provides a promising therapeutic strategy for optimizing oncotherapy. Although erastin is an effective ferroptosis trigger, the potential of its clinical application is largely restricted by its poor water solubility and concomitant limitations.

Whole-exome sequencing reveals the metastatic potential of hepatocellular carcinoma from the perspective of tumor and circulating tumor DNA.

Background: Relapse of hepatocellular carcinoma (HCC) due to vascular invasion is common, but the genomic mechanisms remain unclear, and molecular determinants of high-risk relapse cases are lacking. We aimed to reveal the evolutionary trajectory of microvascular invasion (MVI) and develop a predictive signature for relapse in HCC.

Methods: Whole-exome sequencing was performed on tumor and peritumor tissues, portal vein tumor thrombus (PVTT), and circulating tumor DNA (ctDNA) to compare the genomic profiles between 5 HCC patients with MVI and 5 patients without MVI.

Traditional mineral medicine realgar and potentially exerted therapeutic effects by altering the gut microbiota.

Introduction: Realgar has a long history ofuse in traditional medicines. However, the mechanism through which Realgar or (RIF) exert therapeutic effects is only partially understood.

Methods: In this study, 60 feces and 60 ileum samples from rats administered with realgar or RIF were collected to examine the gut microbiota.

STAU1 promotes adipogenesis by regulating the alternative splicing of Pparγ2 mRNA.

During adipocyte differentiation, specific genes such as peroxisome proliferator-activated receptor γ (PPARγ) are transcribed and post-transcriptional pre-mRNA is processed into mature mRNA. Since Pparγ2 pre-mRNAs contain putative binding sites for STAUFEN1 (STAU1), which can affect the alternative splicing of pre-mRNA, we hypothesized that STAU1 might regulate the alternative splicing of Pparγ2 pre-mRNA. In this study, we found that STAU1 affects the differentiation of 3 T3-L1 pre-adipocytes.

Disruption of SLFN11 Deficiency-Induced CCL2 Signaling and Macrophage M2 Polarization Potentiates Anti-PD-1 Therapy Efficacy in Hepatocellular Carcinoma.

Background & Aims: The therapeutic effect of immune checkpoint inhibitors (ICIs) is poor in hepatocellular carcinoma (HCC) and varies greatly among individuals. Schlafen (SLFN) family members have important functions in immunity and oncology, but their roles in cancer immunobiology remain unclear. We aimed to investigate the role of the SLFN family in immune responses against HCC.

The Effect of Decreased Ca/Mg ATPase Activity on subsp. sp1.1 Survival during Spray Drying.

Compared with the commonly used technique of freeze-drying, spray drying has lower energy costs. However, spray drying also has a fatal disadvantage: a lower survival rate. In this study, the survival of bacteria in a spray-drying tower decreased as the water content was reduced.

A novel murine model of combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Primary liver cancer (PLC) is a common gastrointestinal malignancy worldwide. While hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two major pathologic types of PLC, combined HCC and ICC (cHCC-ICC) is a relatively rare subtype that shares both hepatocyte and cholangiocyte differentiation. However, the molecular feature of this unique tumor remains elusive because of its low incidence and lack of a suitable animal model.

A Novel mRNA Signature Related to Immunity to Predict Survival and Immunotherapy Response in Hepatocellular Carcinoma.

Background And Aims: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the incidence and mortality rates are increasing. Given the limited treatments of HCC and promising application of immunotherapy for cancer, we aimed to identify an immune-related prognostic signature that can predict overall survival (OS) rates and immunotherapy response in HCC.

Methods: The initial signature development was conducted using a training dataset from the Cancer Genome Atlas followed by independent internal and external validations from that resource and the Gene Expression Omnibus.

The relationship between fear of recurrence and depression in patients with cancer: The role of invasive rumination and catastrophizing.

Objective: To examine the relationship between fear of recurrence and depression in patients with cancer.

Materials And Methods: Two hundred and fifty-nine participants completed self-report questionnaires, including the Fear of Progression Questionnaire-Short Form, Rumination Inventory, Cognitive Emotion Regulation Questionnaire (Chinese version), and Center for Epidemiological Studies Depression Scale.

Results: Fear of recurrence in patients with cancer was moderate, and the level of depression was significantly higher than that in the normal population.

Sorafenib-Loaded CuSe Nanoparticles Boost Photothermal-Synergistic Targeted Therapy against Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) accounts for the predominant form of liver malignancy and presents a leading cause of cancer-related death globally. Sorafenib (SOR), a first-line targeted drug for advanced HCC treatment, has a battery of untoward side effects. Photothermal therapy (PTT) has been utilized as an effective adjuvant in synergy with other approaches.

GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism.

Guanosine triphosphate binding protein 4 (GTPBP4) is a key regulator of cell cycle progression and MAPK activation. However, how its biological properties intersect with cellular metabolism in hepatocellular carcinoma (HCC) development remains poorly unexplained. Here, high GTPBP4 expression is found to be significantly associated with worse clinical outcomes in patients with HCC.

Nalidixic acid potentiates the antitumor activity in sorafenib-resistant hepatocellular carcinoma the tumor immune microenvironment analysis.

Sorafenib resistance is often developed and impedes the benefits of clinical therapy in hepatocellular carcinoma (HCC) patients. However, the relationship between sorafenib resistance and tumor immune environment and adjuvant drugs for sorafenib-resistant HCC are not systemically identified. This study first analyzed the expression profiles of sorafenib-resistant HCC cells to explore immune cell infiltration levels and differentially expressed immune-related genes (DEIRGs).

The relationship between childhood trauma and post-traumatic growth among college students: The role of acceptance and positive reappraisal.

Objective: To examine the relationship among childhood trauma, acceptance, positive reappraisal and post-traumatic growth (PTG) among college students.

Methods: Research participants were selected by random cluster sampling. 1,028 college students (62.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells.

Nucleosome remodeling and deacetylation complex and MBD3 influence mouse embryonic stem cell naïve pluripotency under inhibition of protein kinase C.

The pluripotency of naïve mouse embryonic stem cells (mES) is regulated by multiple signaling pathways, with inhibition of protein kinase C (PKCi) playing a particularly important role in maintaining naïve mES. However, the regulatory function of nucleosome remodeling and deacetylase (NuRD) complex in mES cultured in a PKCi system is unknown. We found that, compared with 2iL-derived mES, PKCi-derived mES showed low mRNA expression of NuRD complex subunits, including MBD3, HDAC1/HDAC2, MTA1, and RbAP46/RbAP48.

PKC inhibitors regulate stem cell self-renewal by regulating H3K27me3 and H3K9me3.

Embryonic stem cell (ESC) research is critical to the scientific community, as their application in regenerative medicine can be widely beneficial. ESCs eventually withdraw from their self-renewal program and subsequently differentiate into specific cell lineages; however, the mechanisms regulating these processes remain unclear. PKC inhibition using 3-[1-[3-(dimethylamino) propyl]-5-methoxy-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione (PKCi) is responsible for the derivation and maintenance of human, rat, and mouse ESCs, but the mechanism by which PKCi maintains stem cell self-renewal is poorly understood.