Emerging therapeutic landscape: Incretin agonists in chronic kidney disease management.

The increasing incidence of chronic kidney disease (CKD) poses a significant public health concern, prompting heightened attention to its treatment. Incretins, including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, are intestinal peptides released after nutrient intake, known for their hypoglycemic effects in diabetes management. Recent advancements highlight the promising outcomes of GLP-1 receptor agonists in reducing CKD risk factors and improving renal outcomes. The multifaceted functions of GLP-1, such as its anti-obesity, anti-hypertensive, anti-hyperglycemic, anti-lipid, anti-inflammatory, and endothelial function protective properties, contribute to its potential as a therapeutic agent for CKD. Although experiments suggest the potential benefits of incretin in CKD, a comprehensive understanding of its specific mechanisms is still lacking. This review aims to provide a detailed examination of current evidence and potential future directions, emphasizing the promising yet evolving landscape of incretin agonists in the context of CKD.

Exploring the multi-targeting phytoestrogen potential of Calycosin for cancer treatment: A review.

Cancer remains a significant challenge in the field of oncology, with the search for novel and effective treatments ongoing. Calycosin (CA), a phytoestrogen derived from traditional Chinese medicine, has garnered attention as a promising candidate. With its high targeting and low toxicity profile, CA has demonstrated medicinal potential across various diseases, including cancers, inflammation, and cardiovascular disease. Studies have revealed that CA possesses inhibitory effects against a diverse array of cancers. The underlying mechanism of action involves a reduction in tumor cell proliferation, induction of tumor cell apoptosis, and suppression of tumor cell migration and invasion. Furthermore, CA has been shown to enhance the efficacy of certain chemotherapeutic drugs, making it a potential component in treating malignant tumors. Given its high efficacy, low toxicity, and multi-targeting characteristics, CA holds considerable promise as a therapeutic agent for cancer treatment. The objective of this review is to present a synthesis of the current understanding of the antitumor mechanism of CA and its research progress.

The impact of the senescent microenvironment on tumorigenesis: Insights for cancer therapy.

The growing global burden of cancer, especially among people aged 60 years and over, has become a key public health issue. This trend suggests the need for a deeper understanding of the various cancer types in order to develop universally effective treatments. A prospective area of research involves elucidating the interplay between the senescent microenvironment and tumor genesis. Currently, most oncology research focuses on adulthood and tends to ignore the potential role of senescent individuals on tumor progression. Senescent cells produce a senescence-associated secretory phenotype (SASP) that has a dual role in the tumor microenvironment (TME). While SASP components can remodel the TME and thus hinder tumor cell proliferation, they can also promote tumorigenesis and progression via pro-inflammatory and pro-proliferative mechanisms. To address this gap, our review seeks to investigate the influence of senescent microenvironment changes on tumor development and their potential implications for cancer therapies.

Metabolic diseases and healthy aging: identifying environmental and behavioral risk factors and promoting public health.

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue and cellular functions, along with a significant increase in the risk of various aging-related diseases, including metabolic diseases. While advances in modern medicine have significantly promoted human health and extended human lifespan, metabolic diseases such as obesity and type 2 diabetes among the older adults pose a major challenge to global public health as societies age. Therefore, understanding the complex interaction between risk factors and metabolic diseases is crucial for promoting well-being and healthy aging. This review article explores the environmental and behavioral risk factors associated with metabolic diseases and their impact on healthy aging. The environment, including an obesogenic environment and exposure to environmental toxins, is strongly correlated with the rising prevalence of obesity and its comorbidities. Behavioral factors, such as diet, physical activity, smoking, alcohol consumption, and sleep patterns, significantly influence the risk of metabolic diseases throughout aging. Public health interventions targeting modifiable risk factors can effectively promote healthier lifestyles and prevent metabolic diseases. Collaboration between government agencies, healthcare providers and community organizations is essential for implementing these interventions and creating supportive environments that foster healthy aging.

BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases.

Subcellular organelles dysfunction is implicated in various diseases, including metabolic diseases, neurodegenerative diseases, cancer, and cardiovascular diseases. BAM15, a selective mitochondrial uncoupler, has emerged as a promising therapeutic agent due to its ability to enhance mitochondrial respiration and metabolic flexibility. By disrupting the coupling between electron transport and ATP synthesis, BAM15 dissipates the proton gradient, leading to increased mitochondrial respiration and energy expenditure. This review provides a comprehensive overview of BAM15, including its mechanism of action and potential therapeutic applications in diverse disease contexts. BAM15 has shown promise in obesity by increasing energy expenditure and reducing fat accumulation. In diabetes, it improves glycemic control and reverses insulin resistance. Additionally, BAM15 has potential in non-alcoholic fatty liver disease, sepsis, and cardiovascular diseases by mitigating oxidative stress, modulating inflammatory responses, and promoting cardioprotection. The safety profile of BAM15 is encouraging, with minimal adverse effects and remarkable tolerability. However, challenges such as its high lipophilicity and the need for alternative delivery methods need to be addressed. Further research is necessary to fully understand the therapeutic potential of BAM15 and optimize its application in clinical settings.

Secreted frizzled-related proteins: A promising therapeutic target for cancer therapy through Wnt signaling inhibition.

The Wnt signaling system is a critical pathway that regulates embryonic development and adult homeostasis. Secreted frizzled-related proteins (SFRPs) are extracellular inhibitors of Wnt signaling that act by binding directly to Wnt ligands or Frizzled receptors. SFRPs can act as anti-Wnt agents and suppress cancer growth by blocking the action of Wnt ligands. However, SFRPs are often silenced by promoter methylation in cancer cells, resulting in hyperactivation of the Wnt pathway. Epigenetic modifiers can reverse this silencing and restore SFRPs expression. Despite the potential of SFRPs as a therapeutic target, the effects of SFRPs on tumor development remain unclear. Therefore, a review of the expression of various members of the SFRPs family in different cancers and their potential as therapeutic targets is warranted. This review aims to summarize the current knowledge of SFRPs in cancer, focusing on their expression patterns and their potential as novel therapeutic targets.

Global, Regional, and National Burden of Pancreatic Cancer, 1990-2019: Results from the Global Burden of Disease Study 2019.

Aims: Pancreatic cancer (PC) is a malignant tumor with a strong invasive nature and low survival rate. We aimed to estimate the PC burden at the global, regional, and national levels in 204 countries from 1990 to 2019. Methods: Detailed data, including the incidence, death, and disability-adjusted life years (DALYs), were analyzed from the Global Burden of Diseases Study 2019. Results: Globally, there were 530,297 (486,175-573,635) incident cases and 531,107 (491,948-566,537) deaths from PC in 2019. The age-standardized incidence rate (ASIR) was 6.6 (6-7.1), and the age-standardized mortality rate (ASMR) was 6.6 (6.1-7.1) per 100,000 person-years. PC caused 11,549,016 (10,777,405-12,338,912) DALYs, with an age-standardized rate of 139.6 (130.2-149.1) per 100,000 person-years. There were increases in estimated annual percentage changes (EAPCs) of ASIR (0.83; 0.78-0.87), ASMR (0.77; 0.73-0.81), and age-standardized DALYs rate (ASDR) (0.67; 0.63-0.71). The global number of incident cases increased by 168.7%, from 197,348 (188,604-203,971) to 530,297 (486,175-573,635); the number of deaths increased by 168.2% from 198,051 (189,329-204,763) to 531,107 (491,948-566,537); and total DALYs increased by 148.5% from 4,647,207 (4,465,440-4,812,129) to 11,549,016 (10,777,405-12,338,912). East Asia and China recorded the highest number of incident cases, deaths, and DALYs. The proportion of deaths was attributable to smoking (21.4%), elevated fasting glucose (9.1%), and high BMI (6%). Conclusions: Our study updated the epidemiological trends and risk factors for PC. PC remains a major hazard to the sustainability of health systems worldwide, with an increasing incidence rate and mortality from 1990 to 2019. More targeted strategies are required to prevent and treat PC.

NTRK fusions in thyroid cancer: Pathology and clinical aspects.

Thyroid cancer is the most common endocrine cancer. Neurotrophic tyrosine receptor kinase (NTRK) fusions are oncogenic drivers in multiple solid tumors, including thyroid cancer. NTRK fusion thyroid cancer has unique pathological features such as mixed structure, multiple nodes, lymph node metastasis, and a background of chronic lymphocytic thyroiditis. Currently, RNA-based next-generation sequencing is the gold standard for the detection of NTRK fusions. Tropomyosin receptor kinase inhibitors have shown promising efficacy in patients with NTRK fusion-positive thyroid cancer. Efforts to overcome acquired drug resistance are the focus of research concerning next-generation TRK inhibitors. However, there are no authoritative recommendations or standardized procedures for the diagnosis and treatment of NTRK fusions in thyroid cancer. This review discusses current research progress regarding NTRK fusion-positive thyroid cancer, summarizes the clinicopathological features of the disease, and outlines the current statuses of NTRK fusion detection and targeted therapeutic agents.

Advances in understanding the role and mechanisms of tumor stem cells in HER2-positive breast cancer treatment resistance (Review).

Approximately 15-20% of breast carcinomas exhibit human epidermal growth factor receptor (HER2) protein overexpression. HER2-positive breast cancer (BC) is a heterogeneous and aggressive subtype with poor prognosis and high relapse risk. Although several anti-HER2 drugs have achieved substantial efficacy, certain patients with HER2-positive BC relapse due to drug resistance after a treatment period. There is increasing evidence that BC stem cells (BCSCs) drive therapeutic resistance and a high rate of BC recurrence. BCSCs may regulate cellular self-renewal and differentiation, as well as invasive metastasis and treatment resistance. Efforts to target BCSCs may yield new methods to improve patient outcomes. In the present review, the roles of BCSCs in the occurrence, development and management of BC treatment resistance were summarized; BCSC-targeted strategies for the treatment of HER2-positive BC were also discussed.

Global burden of non-alcoholic fatty liver disease in 204 countries and territories from 1990 to 2019.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic linked to metabolic disease and is the most prevalent cause of chronic liver disease. We, therefore, designed the study to analyze the global and regional burden of NAFLD from 1990 to 2019. METHODS: We collected data on NAFLD from the Global Burden of Disease study 2019, aiming to conduct a systematic assessment of the changes and trends in NAFLD in 204 countries. Secondary analysis of NAFLD was conducted using age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) to show the changing trends and development characteristics. Data statistics and visualization were executed with the R program. RESULTS: Globally, incidence, deaths and disability-adjusted life years (DALYs) of NAFLD all showed an upward trend. Between 1990 and 2019, the incidence of NAFLD increased by 95.4%, from 88,177 to 172,330 cases. Meanwhile, the ASIR of the middle SDI region had the highest increase, followed by the low-middle SDI region. Of all countries, the most incident cases were in China, which accounted for approximately 23.6% of NAFLD. China was also the country with the largest cases of deaths and DALYs. And behavioral risk, metabolic factors, smoking and high fasting plasma glucose were the critical risk factors associated with the mortality and DALYs of NAFLD. CONCLUSION: NAFLD has become a considerable health burden in many countries. Therefore, we should control the risk factors of NAFLD and take corresponding measures to achieve its early prevention and treatment.

Irisin protects against obesity-related chronic kidney disease by regulating perirenal adipose tissue function in obese mice.

BACKGROUND: Compared with typical visceral fat deposits in obesity and metabolic syndrome, perirenal adipose tissue (PRAT) dysfunction is more closely linked to obesity-related chronic kidney disease (OB-CKD). The myokine irisin reportedly promotes positive outcomes in metabolic disease. This study investigated whether irisin could reduce urinary albumin excretion and demonstrate renoprotective effects through the regulation of PRAT function in obese mice. METHODS: C57BL/6 J mice received a high-fat diet (HFD) with or without concurrent administration of irisin. Glucose tolerance, plasma levels of free fatty acids, and urinary albumin excretion were assessed, along with renal morphology. The vascular endothelial growth factor and nitric oxide in glomeruli were also analyzed, in addition to PRAT function-associated proteins. RESULTS: Irisin administration significantly reduced the final body weight, fat mass, and free fatty acids, without reducing PRAT mass, in HFD mice. Furthermore, irisin decreased urinary albumin excretion and attenuated both renal fibrosis and lipid accumulation. Irisin administration led to increases in PRAT function-associated proteins, including sirtuin1, uncoupling protein-1, and heme-oxygenase-1. Ex vivo treatment of PRAT and glomeruli with irisin also restored PRAT function. Finally, irisin treatment restored the vascular endothelial growth factor-nitric oxide axis. CONCLUSIONS: Irisin attenuated metabolic disorders and protected against OB-CKD by normalizing the PRAT-kidney axis. These results suggest that agents targeting PRAT activation might be useful for treatment of OB-CKD.

The Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus.

Mesenchymal stem cells (MSCs) exist in many tissues and can differentiate into cells of multiple lineages, such as adipocytes, osteoblasts, or chondrocytes. MSC administration has demonstrated therapeutic potential in various degenerative and inflammatory diseases (e.g., graft-vs.-host disease, multiple sclerosis, Crohn's disease, organ fibrosis, and diabetes mellitus [DM]). The mechanisms involved in the therapeutic effects of MSCs are multifaceted. Generally, implanted MSCs can migrate to sites of injury, where they establish an anti-inflammatory and regenerative microenvironment in damaged tissues. In addition, MSCs can modulate innate and adaptive immune responses through immunosuppressive mechanisms that involve immune cells, inflammatory cytokines, chemokines, and immunomodulatory factors. DM has a high prevalence worldwide; it also contributes to a high rate of mortality worldwide. MSCs offer a promising therapeutic agent to prevent or repair damage from DM and diabetic complications through properties such as multilineage differentiation, homing, promotion of angiogenesis, and immunomodulation (e.g., prevention of oxidative stress, fibrosis, and cell death). In this study, we review current findings regarding the immunomodulatory and regenerative mechanisms of MSCs, as well as their therapeutic applications in DM and DM-related complications.

COL1A1: A novel oncogenic gene and therapeutic target in malignancies.

Collagen type I alpha 1 (COL1A1), a member of the collagen family, is involved in epithelial-mesenchymal transition, which is closely linked to malignant tumorigenesis. COL1A1 is highly expressed in various cancers and regulates various cellular processes, including cell proliferation, metastasis, apoptosis, and cisplatin resistance. COL1A1 is also associated with cancer progression and prognosis; elevated COL1A1 expression is associated with poor prognosis in cancer patients. However, the main role of COL1A as a cancer-promoting factor in specific tumors has not been reported. Additionally, the protein levels and mechanisms of action of this protein differ among tumor types. This review discusses current research progress concerning COL1A1 in different tumor types, and then summarizes its contributions to cancer progression, thus providing a basis for follow-up research and potential targets for cancer treatment.

Post-Translational Modifications of p53 in Ferroptosis: Novel Pharmacological Targets for Cancer Therapy.

The tumor suppressor p53 is a well-known cellular guardian of genomic integrity that blocks cell cycle progression or induces apoptosis upon exposure to cellular stresses. However, it is unclear how the remaining activities of p53 are regulated after the abrogation of these routine activities. Ferroptosis is a form of iron- and lipid-peroxide-mediated cell death; it is particularly important in p53-mediated carcinogenesis and corresponding cancer prevention. Post-translational modifications have clear impacts on the tumor suppressor function of p53. Here, we review the roles of post-translational modifications in p53-mediated ferroptosis, which promotes the elimination of tumor cells. A thorough understanding of the p53 functional network will be extremely useful in future strategies to identify pharmacological targets for cancer therapy.

Thyroid Cancer and COVID-19: Prospects for Therapeutic Approaches and Drug Development.

Thyroid cancer is the most prevalent endocrine malignancy and the reported incidence of thyroid cancer has continued to increase in recent years. Since 2019, coronavirus disease 2019 (COVID-19) has been spreading worldwide in a global pandemic. COVID-19 aggravates primary illnesses and affects disease management; relevant changes include delayed diagnosis and treatment. The thyroid is an endocrine organ that is susceptible to autoimmune attack; thus, thyroid cancer after COVID-19 has gradually attracted attention. Whether COVID-19 affects the diagnosis and treatment of thyroid cancer has also attracted the attention of many researchers. This review examines the literature regarding the influence of COVID-19 on the pathogenesis, diagnosis, and treatment of thyroid cancer; it also focuses on drug therapies to promote research into strategies for improving therapy and management in thyroid cancer patients with COVID-19.

Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells.

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway.