Mechanoregulation of angiopoietin-like 4 in epithelial-mesenchymal transition and cancer metastasis

The epithelial-mesenchymal transition (EMT) serves as a pivotal mechanism in the progression of metastatic cancer. However, current research, predominantly reliant on 2D monolayer cultures, inadequately replicates the intricate nature of a 3D tumor microenvironment. In the main project (Paper I), we investigated the transcriptomes of various cancer cell types undergoing EMT in both 2D and 3D cultures with different EMT inducers. We identified a 3D EMT gene signature that has broad implications across different types of human cancers. Angiopoietin-like 4 protein (ANGPTL4) was found to be a top ranked hub gene with clinical relevance and impact. Our study also revealed the mechanoregulation of ANGPTL4, which corroborated with its high expression in advanced tumors. Consistently, ANGPTL4 deficiency attenuated primary tumor growth and EMT of cancer cells. These findings suggest that targeting ANGPTL4 may be a promising approach to inhibit EMT and prevent cancer progression. In the collaborative project (Paper II), we studied the regulation of membrane microenvironment and signal transduction in natural killer (NK) cells, a group of innate immune cells involved in the tumor microenvironment (TME) and cancer immunotherapy. Here, we revealed the PIP2-regulated recruitment of DAP12 homodimer to lipid raft boundary of NK cells. In another collaborative project (Paper III), we introduce HTCA, a single-cell RNA-sequencing database with various user-friendly analysis tools. Collectively, our main findings reflect the intricate regulation of physical stiffness within the TME influencing EMT signaling in cancer cells, where ANGPTL4 emerges as a crucial player. Our comprehensive analyses strongly underscore the clinical significance of ANGPTL4, particularly in advanced stage cancer, aligning with our broader understanding of tumors in patients. In essence, our study vividly demonstrates how the TME's stiffness orchestrates the mechanoregulation of ANGPTL4, a hub gene within the 3D EMT gene signature

MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues

Sarcomas are deadly malignant tumors of mesenchymal origin occurring at all ages. The expression and function of the membrane-type matrix metalloproteinase MMP14 is closely related to the mesenchymal cell phenotype, and it is highly expressed in most sarcomas. MMP14 regulates the activity of multiple extracellular and plasma membrane proteins, influencing cell–cell and cell–extracellular matrix (ECM) communication. This regulation mediates processes such as ECM degradation and remodeling, cell invasion, and cancer metastasis. Thus, a comprehensive understanding of the biology of MMP14 in sarcomas will shed light on the mechanisms controlling the key processes in these diseases. Here, we provide an overview of the function and regulation of MMP14 and we discuss their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas

Effect of Heat-Producing Needling Technique on the Local Skin Temperature: Clinical Dataset

The heat-producing needling technique is a special compound manipulating procedure on the acupuncture needle which has been recorded to produce a warm sensation in the body in ancient TCM literature. This randomized, subject-blinded clinical study was performed to examine the effect of heat-producing acupuncture treatment on the ST36 local skin temperature. A total of 30 healthy participants received four successive sessions of heat-producing acupuncture treatment, non-acupoint heat-producing acupuncture treatment, normal stable acupuncture treatment, and non-invasive sham acupuncture treatment at the ST36 acupoint in a random sequence. Within each session, the local ST36 skin temperature and basal body temperature of each participant were measured at 1 min before needle insertion, just after needle insertion and manipulation (if any), 5 min after needle insertion with needle removal immediately after temperature taking, and 5 min after needle removal. Furthermore, the participants were also required to declare their needling and heat sensation felt during the acupuncture needling treatment period using a visual analogue scale from 1 to 10 immediately after each treatment session. This data descriptor presents all the clinical data obtained in the above mentioned study

Reactive oxygen species: a volatile driver of field cancerization and metastasis

Abstract Field cancerization and metastasis are the leading causes for cancer recurrence and mortality in cancer patients. The formation of primary, secondary tumors or metastasis is greatly influenced by multifaceted tumor-stroma interactions, in which stromal components of the tumor microenvironment (TME) can affect the behavior of the cancer cells. Many studies have identified cytokines and growth factors as cell signaling molecules that aid cell to cell communication. However, the functional contribution of reactive oxygen species (ROS), a family of volatile chemicals, as communication molecules are less understood. Cancer cells and various tumor-associated stromal cells produce and secrete a copious amount of ROS into the TME. Intracellular ROS modulate cell signaling cascades that aid in the acquisition of several hallmarks of cancers. Extracellular ROS help to propagate, amplify, and effectively create a mutagenic and oncogenic field which facilitate the formation of multifoci tumors and act as a springboard for metastatic tumor cells. In this review, we summarize our current knowledge of ROS as atypical paracrine signaling molecules for field cancerization and metastasis. Field cancerization and metastasis are often discussed separately; we offer a model that placed these events with ROS as the focal instigating agent in a broader “seed-soil” hypothesis

Children with type 1 diabetes in COVID-19 pandemic: difficulties and solutions

Children/adolescents with type 1 diabetes (T1D) require holistic approach and continuous care. However, the coronavirus disease 2019 (COVID-19) pandemic has made challenges for the T1D children and their caregivers, professionals, and the healthcare system. This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic. T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide, which deserves a public concern particularly in the COVID-19 pandemic. As reported in previous studies, T1D is a risk factor related to severe cases, while the virus may induce new-onset diabetes and serious complications. Moreover, restriction strategies influence medical availability and lifestyle, impact glycemic control and compilation management, and thus pose stress on families and health providers of youths with T1D, especially on those with certain fragile conditions. Therefore, special treatment plans are required for children provided by caregivers and the local health system. Latest health tools such as improved medical devices and telemedicine service, as well as a combined support may benefit in this period. This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic. Therefore, strategies are supposed to be formulated to mitigate the difficulties and stress among this group, particularly in the most at-risk population. Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations.Published versio

Cancer-associated fibroblasts in tumor microenvironment - accomplices in tumor malignancy

There is much cellular heterogeneity in the tumor microenvironment. The tumor epithelia and stromal cells co-evolve, and this reciprocal relationship dictates almost every step of cancer development and progression. Despite this, many anticancer therapies are designed around druggable features of tumor epithelia, ignoring the supportive role of stromal cells. Cancer-associated fibroblasts (CAFs) are the dominant cell type within the reactive stroma of many tumor types. Numerous previous studies have highlighted a pro-tumorigenic role for CAFs via secretion of various growth factors, cytokines, chemokines, and the degradation of extracellular matrix. Recent works showed that CAFs secrete H2O2 to effect stromal-mediated field cancerization, transform primary epithelial cells, and aggravate cancer cell aggressiveness, in addition to inflammatory and mitogenic factors. Molecular characterization of CAFs also underscores the importance of Notch and specific nuclear receptor signaling in the activation of CAFs. This review consolidates recent findings of CAFs and highlights areas for future investigations.Ministry of Education (MOE)Accepted versionAuthors’ works described in this article were supported by grants from Ministry of Education, Singapore (MOE2014-T2-1-012, MOE2012-T1-001-036 and AcRF Tier 1 RG134/15) to NST

Diabetes and sarcopenic obesity : pathogenesis, diagnosis, and treatments

Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity.Published versio

Cellular Senescence: Mechanisms and Therapeutic Potential

Cellular senescence is a complex and multistep biological process which cells can undergo in response to different stresses. Referring to a highly stable cell cycle arrest, cellular senescence can influence a multitude of biological processes—both physiologically and pathologically. While phenotypically diverse, characteristics of senescence include the expression of the senescence-associated secretory phenotype, cell cycle arrest factors, senescence-associated β-galactosidase, morphogenesis, and chromatin remodelling. Persistent senescence is associated with pathologies such as aging, while transient senescence is associated with beneficial programmes, such as limb patterning. With these implications, senescence-based translational studies, namely senotherapy and pro-senescence therapy, are well underway to find the cure to complicated diseases such as cancer and atherosclerosis. Being a subject of major interest only in the recent decades, much remains to be studied, such as regarding the identification of unique biomarkers of senescent cells. This review attempts to provide a comprehensive understanding of the diverse literature on senescence, and discuss the knowledge we have on senescence thus far

PPAR-α modulators as current and potential cancer treatments

Cancer is one of the leading causes of mortality worldwide. PPAR modulators may hold great potential for the management of cancer patients. Indeed, PPARs are critical sensors and regulators of lipid, and they are able to promote eNOS activation, regulate immunity and inflammation response, and affect proliferation and differentiation of cancer cells. Cancer, a name given to a group of diseases, is characterized by multiple distinctive biological behaviors, including angiogenesis, abnormal cell proliferation, aerobic glycolysis, inflammation, etc. In the last decade, emerging evidence has shown that PPAR-α, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. Therefore, the multi-functional PPAR modulators have substantial promise in various types of cancer therapies. This review aims to consolidate the functions of PPAR-α, as well as discuss the current and potential applications of PPAR-α agonists and antagonists in tackling cancer.Published versionThis work was funded by the National Natural Science Foundation of China (Grant No. 31800652), Young Scientist Program by Beijing University of Chinese Medicine (Grant No. BUCM-2019-QNKXJ-C014), the Double First Class Construction Funds of Discipline of Integrated Traditional Chinese and Western Medicine of Beijing University of Chinese Medicine, the Young Elite Scientists Sponsorship Program by CAST (Project No: CACM-2018-QNRC2-C06)

From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research

Diabetes, a silent killer, is one of the most widely prevalent conditions of the present time. According to the 2017 International Diabetes Federation (IDF) statistics, the global prevalence of diabetes among the age group of 20–79 years is 8.8%. In addition, 1 in every 2 persons is unaware of the condition. This unawareness and ignorance lead to further complications. Pre-diabetes is the preceding condition of diabetes, and in most of the cases, this ultimately leads to the development of diabetes. Diabetes can be classified into three types, namely type 1 diabetes, type 2 diabetes mellitus (T2DM) and gestational diabetes. The diagnosis of both pre-diabetes and diabetes is based on glucose criteria; the common modalities used are fasting plasma glucose (FPG) test and oral glucose tolerance test (OGTT). A glucometer is commonly used by diabetic patients to measure blood glucose levels with fast and rather accurate measurements. A few of the more advanced and minimally invasive modalities include the glucose-sensing patch, SwEatch, eyeglass biosensor, breath analysis, etc. Despite a considerable amount of data being collected and analyzed regarding diabetes, the actual molecular mechanism of developing type 2 diabetes mellitus (T2DM) is still unknown. Both genetic and epigenetic factors are associated with T2DM. The complications of diabetes can predominantly be classified into two categories: microvascular and macrovascular. Retinopathy, nephropathy, and neuropathy are grouped under microvascular complications, whereas stroke, cardiovascular disease, and peripheral artery disease (PAD) belong to macrovascular complications. Unfortunately, until now, no complete cure for diabetes has been found. However, the treatment of pre-diabetes has shown significant success in preventing the further progression of diabetes. To prevent pre-diabetes from developing into T2DM, lifestyle intervention has been found to be very promising. Various aspects of diabetes, including the aforementioned topics, have been reviewed in this paper