Having a hypoxic microenvironment is a common and salient feature of most solid tumors. Hypoxia has a profound effect on the biological behavior and malignant phenotype of cancer cells, mediates the effects of cancer chemotherapy, radiotherapy, and immunotherapy through complex mechanisms, and is closely associated with poor prognosis in various cancer patients. Accumulating studies have demonstrated that through normalization of the tumor vasculature, nanoparticle carriers and biocarriers can effectively increase the oxygen concentration in the tumor microenvironment, improve drug delivery and the efficacy of radiotherapy. They also increase infiltration of innate and adaptive anti-tumor immune cells to enhance the efficacy of immunotherapy. Furthermore, drugs targeting key genes associated with hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, and drugs targeting hypoxia-inducible factors and downstream targets, can be used for visualization and quantitative analysis of tumor hypoxia and antitumor activity. However, the relationship between hypoxia and cancer is an area of research that requires further exploration. Here, we investigated the potential factors in the development of hypoxia in cancer, changes in signaling pathways that occur in cancer cells to adapt to hypoxic environments, the mechanisms of hypoxia-induced cancer immune tolerance, chemotherapeutic tolerance, and enhanced radiation tolerance, as well as the insights and applications of hypoxia in cancer therapy.

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Betulinic acid (BA) is a pentacyclic triterpene compound that can be obtained by separation, chemical synthesis and biotransformation from birch. BA has antitumour activity, and its mechanisms of action mainly include the induction of mitochondrial oxidative stress; the regulation of specificity protein transcription factors, and the inhibition of signal transducer and activator of transcription 3 and nuclear factor-κB signalling pathways. In addition, BA can increase the sensitivity of cancer cells to other chemotherapy drugs. Recent studies have shown that BA plays an anticancer role in several kinds of tumour diseases. In this article, the anticancer mechanism of BA and its application in the treatment of tumour diseases are reviewed.

Gastric cancer is a highly aggressive malignancy characterized by a complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are a key component of the TME, exhibit significant heterogeneity and play crucial roles in tumor progression. Therefore, a comprehensive understanding of CAFs is essential for developing novel therapeutic strategies for gastric cancer. This study investigates the characteristics and functional information of CAF subtypes and explores the intercellular communication between CAFs and malignant epithelial cells (ECs) in gastric cancer by analyzing single-cell sequencing data from 24 gastric cancer samples. CellChat was employed to map intercellular communication, and Seurat was used to integrate single-cell sequencing data with spatial transcriptome data to reconstruct a comprehensive single-cell spatial map. The spatial relationship between apCAFs and cancer cells was analyzed using multicolor immunohistochemistry. Cells were categorized into nine distinct categories, revealing a positive correlation between the proportions of epithelial cells (ECs) and fibroblasts. Furthermore, six fibroblast subpopulations were identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle cells (SMCs), and proliferative CAFs (pCAFs). Each of these subpopulations was linked to various biological processes and immune responses. Malignant ECs exhibited heightened intercellular communication, particularly with CAF subpopulations, through specific ligand-receptor interactions. High-density regions of CAF subpopulations displayed spatial exclusivity, with pericytes serving as a source for iCAFs, mCAFs, and apCAFs. Notably, malignant ECs and apCAFs showed increased interactions, with certain ligand-receptor pairs potentially impacting the prognosis of gastric cancer. Multiplex immunohistochemistry (mIHC) confirmed the close spatial proximity of apCAFs to cancer cells in gastric cancer. Our study provided a comprehensive characterization of CAF heterogeneity in gastric cancer and revealed the intricate intercellular networks within the TME. The identified CAF subpopulations and their interactions with malignant cells could serve as potential therapeutic targets.

Background: Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data. Methods: Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index. Results: Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased. Conclusions: The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.