OBJECTIVE: This study aims to understand the role of cirrhosis in promoting hepatocellular carcinoma (HCC) progression by analyzing the differential expression of long noncoding RNAs (lncRNAs) between cirrhotic hepatocellular carcinoma (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC).
METHODS: A transcriptional profile array was used to identify differentially expressed lncRNAs. Subsequently, a specific lncRNA was selected to evaluate the clinical significance, potential functions, regulatory targets, and pathways through both in vitro and in vivo experiments.
RESULTS: The study identified a lncRNA, which we termed DERCNC, an acronym for Differentially Expressed RNA between Cirrhotic and Non-Cirrhotic HCC. DERCNC was significantly more highly expressed in CHCC than in NCHCC. Clinically, elevated levels of DERCNC expression were positively correlated with both the cirrhotic state and tumor stage and inversely correlated with tumor differentiation. Furthermore, high expression of DERCNC was associated with a poor prognosis for patients. Conditioned medium from the hepatic stellate cell (LX2) was found to enhance DERCNC expression, SOX9 expression, and tumor proliferation. Overexpression of DERCNC similarly promoted tumor proliferation and increased SOX9 levels. Conversely, DERCNC silencing resulted in the opposite effects. Moreover, the pro-proliferative function of DERCNC was reversible through the modulation of SOX9 expression. Further mechanistic studies revealed that DERCNC upregulated SOX9 by increasing the enrichment of H3K27ac modifications near the SOX9 promoter.
CONCLUSIONS: In conclusion, DERCNC expression in CHCC has significant clinical implications and can aggravate tumor proliferation by targeting SOX9. This represents a novel mechanism by which cirrhosis promotes tumor progression.

Chlorogenic acid (CHA) is a phenolic substance found in various edible plants, such as tea and green coffee extracts. This chemical has demonstrated significant efficacy in reducing the probability of many diseases in preclinical and clinical environments. Chlorogenic acid (CHA) possesses several pharmacological attributes, such as anticancer, hepatoprotective, antimicrobial, immune-suppressant, antioxidant, and antidiabetic activities. Its applications extend to multiple industries, such as food, chemicals, medicine, and healthcare. Studies have shown that CHA can exert its anticancer effects through numerous mechanisms. It can hinder the process of cell division, trigger cell apoptosis, and suppress an increase in cancerous cell growth. The literature research conducted for this study revealed a variety of molecular and cellular processes influencing distinct signaling pathways. These mechanisms include angiogenesis, invasion and migration, oxidative stress, inflammation, cell cycle arrest, and proliferation.However, significant issues surround the use of CHA, primarily due to its limited bioavailability in animal models. This review focuses on the chemistry, natural sources, pharmacokinetics, and underlying mechanisms of action of CHA and its clinical utility in treating life-threatening diseases, such as cancer. The manuscript provides insight into novel formulation approaches.

From molecular and cellular perspectives, heart failure is caused by the loss of cardiomyocytes-the fundamental contractile units of the heart. Because mammalian cardiomyocytes exit the cell cycle shortly after birth, the cardiomyocyte damage induced by myocardial infarction (MI) typically leads to dilatation of the left ventricle (LV) and often progresses to heart failure. However, recent findings indicate that the hearts of neonatal pigs completely regenerated the cardiomyocytes that were lost to MI when the injury occurred on postnatal day 1 (P1). This recovery was accompanied by increases in the expression of markers for cell-cycle activity in cardiomyocytes. These results suggest that the repair process was driven by cardiomyocyte proliferation. This review summarizes findings from recent studies that found evidence of cardiomyocyte proliferation in 1) the uninjured hearts of newborn pigs on P1, 2) neonatal pig hearts after myocardial injury on P1, and 3) the hearts of pigs that underwent apical resection surgery (AR) on P1 followed by MI on postnatal day 28 (P28). Analyses of cardiomyocyte single-nucleus RNA sequencing data collected from the hearts of animals in these three experimental groups, their corresponding control groups, and fetal pigs suggested that although the check-point regulators and other molecules that direct cardiomyocyte cell-cycle progression and proliferation in fetal, newborn, and postnatal pigs were identical, the mechanisms that activated cardiomyocyte proliferation in response to injury may differ from those that regulate cardiomyocyte proliferation during development.

BACKGROUND: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated.
OBJECTIVE: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells.
METHODS: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3β/β-catenin signaling pathway was detected by Western Blot.
RESULTS: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3β(Ser9), β-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells.
CONCLUSIONS: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3β/β-catenin signaling pathway.

BACKGROUND: China now has the highest number of diabetes in the world. Angiotensin II (Ang II) causes insulin resistance by acting on the insulin signaling pathway of peripheral target tissues. However, its effect on islet β-cells remains unclear. The possible role of Angiotensin-( 1-7) [Ang-(1-7)] as an antagonist to the effects of Ang II and in treating diabetes needs to be elucidated.
OBJECTIVE: To assess the effects of Ang II and Ang-(1-7) on the function and growth of islet β cell line NIT-1, which is derived from the islets of non-obese diabetic/large T-antigen (NOD/LT) mice with insulinoma.
METHODS: NIT-1 cells were treated with Ang II, Ang-(1-7) and their respective receptor antagonists. The impact on cell function and growth was then evaluated.
RESULTS: Ang II significantly reduced insulin-stimulated IR-β-Tyr and Akt-Ser; while Ang-(1-7), saralasin (an Ang II receptor antagonist), and diphenyleneiodonium [DPI, a nicotinamide adenine dinucleotide phosphate oxidase (NOX) antagonist] reversed the inhibiting effect. Conversely, Ang II significantly increased insulin-stimulated intracellular H2O2 and P47 phox, while saralasin and DPI reverted the effect. Furthermore, Ang-(1-7) reduced the elevated concentrations of ROS and MDA while increasing the proliferation rate that was reduced by high glucose, all of which were reversed by A-779, an antagonist of the Mas receptor (MasR).
CONCLUSIONS: Angiotensin II poses a negative regulatory effect on insulin signal transduction, increases oxidative stress, and may inhibit the transcription of insulin genes stimulated by insulin in NIT-1 cells. Meanwhile, angiotensin-(1-7) blocked these effects via MasR. These results corroborate the rising potential of the renin-angiotensin system (RAS) in treating diabetes.

Periodontal ligament stem cells (PDLSCs) are important candidate seed cells for alveolar bone tissue engineering. Dasatinib is a tyrosine kinase inhibitor, and its influence on the osteogenic differentiation of mesenchymal stem cells is a controversial topic. The present study explored the effects of different concentrations of dasatinib on the proliferation and osteogenic differentiation of PDLSCs and tentatively revealed the related mechanism. The results of CCK8 showed that low concentrations of dasatinib (1 nM) did not affect proliferation, while high concentrations of dasatinib significantly inhibited the proliferative activity of PDLSCs. This could be related to the inhibiting effects of dasatinib on Erk signals. ALP staining, alizarin red staining, and western blot proved that low concentrations of dasatinib (1 nM) promoted the osteogenic differentiation of PDLSCs, while high concentrations of dasatinib inhibited it. The negative effects of dasatinib on osteogenic differentiation were reversed when EID3 was knocked down, suggesting that EID3 mediates the regulation of dasatinib on the osteo-differentiation of PDLSCs. Taken together, high concentrations of dasatinib inhibited the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals, while low concentrations of dasatinib could be a potential method to enhance the bone regeneration ability of PDLSCs.

OBJECTIVE: At present, cartilage repair does not offer ideal efficacy. Fortunately, recent studies have claimed that RADA-16 peptide is an attractive therapeutic strategy for repairing cartilage defects. Therefore, this study tried to explore the effect of RADA-16 loaded with transforming growth factor-beta (TGF-β) 1 on cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs).
METHODS: First, the RADA-16 peptide was synthesized by solid phase peptide, and a well-defined hydrogel was formed by supramolecular peptide self-assembly. Then, TGF-β1 (loading concentration of 10 ng/mL) was loaded into RADA-16, with scanning electron microscopy to observe the morphology of the TGF-β1/RADA-16 hydrogel and detect its related properties. Next, BMSCs were isolated from bone marrow samples and identified. TGF-β1/RADA-16 was co-cultured with L929, BMSCs, and C28/I2 cells, respectively, and the survival and proliferation ability of the cells was determined by live/dead cell staining and MTT assay. Chondrogenic differentiation and sGAG production of BMSCs were determined by Alcian blue staining and Blyscan assay, the expression of cartilage-associated genes by qRT-PCR, and the levels of inflammatory factors by ELISA. As for mechanism investigation, the Smad and ERK/MAPK signaling pathways were detected by western blot.
RESULTS: RADA-16 hydrogel exhibited a well-distributed and interconnected porous surface structure, with a loading rate of 91.9% for TGF-β1. The TGF-β1/RADA-16 hydrogel had good release and degradation properties, and had no negative effect on the survival and proliferation ability of BMSCs, L929, and C28/I2 cells. Importantly, TGF-β1/RADA-16 hydrogel significantly accelerated chondrogenic differentiation and sGAG generation in BMSCs, and decreased pro-inflammatory factor production. In addition, the hydrogel also significantly activated the Smad and ERK/MAPK pathways of BMSCs.
CONCLUSIONS: RADA-16 loaded with TGF-β1 has good biological properties and can enhance the chondrogenic differentiation ability of BMSCs.

Cancer is characterized by disrupted molecular variables caused by cells that deviate from regular signal transduction. The uncontrolled segment of such cancerous cells annihilates most of the tissues that contact them. Gene therapy, immunotherapy, and nanotechnology advancements have resulted in novel strategies for anticancer drug delivery. Furthermore, diverse dispersion of nanoparticles in normal stroma cells adversely affects the healthy cells and disrupts the crosstalk of tumour stroma. It can contribute to cancer cell progression inhibition and, conversely, to acquired resistance, enabling cancer cell metastasis and proliferation. The tumour\'s microenvironment is critical in controlling the dispersion and physiological activities of nano-chemotherapeutics which is one of the targeted drug therapy. As it is one of the methods of treating cancer that involves the use of medications or other substances to specifically target and kill off certain subsets of malignant cells. A targeted therapy may be administered alone or in addition to more conventional methods of care like surgery, chemotherapy, or radiation treatment. The tumour microenvironment, stromatogenesis, barriers and advancement in the drug delivery system across tumour tissue are summarised in this review.

The abuse and incorrect administration of antibiotics has resulted in an increased proliferation of bacteria that exhibit drug resistance. The emergence of resistant bacteria has become one of the biggest health concerns globally, and an enormous effort has been made to combat them. However, despite the efforts, the emergence of resistant strains is rapidly increasing, while the discovery of new classes of antibiotics has lagged. For this reason, it is pivotal to acquire a more detailed knowledge of bacterial resistance mechanisms and the mechanism of action of substances with antibacterial effects to identify biomarkers, therapeutic targets, and the development of new antibiotics. Metabolomics and proteomics, combined with mass spectrometry for data acquisition, are suitable techniques and have already been applied successfully. This review presents basic aspects of the metabolomic and proteomic approaches and their application for the elucidation of bacterial resistance mechanisms.

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