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Exercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential.

BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome marked by progressive skeletal muscle wasting, systemic inflammation, reduced quality of life, and poor clinical outcomes. Interleukin-6 (IL-6) is a central mediator in cachexia pathophysiology, driving inflammatory signaling, catabolic metabolism, and muscle atrophy. However, IL-6 also rises transiently during exercise, where it exerts beneficial metabolic and anti-inflammatory effects, highlighting the context-dependent nature of IL-6 signaling. MAIN BODY: This review summarizes current knowledge on the regulation and functio

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… In adipose tissue, IL-6 promotes lipolysis (HSL, ATGL), inhibits lipogenesis, drives browning (UCP1, PGC-1α), and induces insulin resistance through SOCS3-mediated inhibition of insulin signaling. … In adipose tissue, IL-6 promotes lipolysis (HSL, ATGL), inhibits lipogenesis, drives browning (UCP1, PGC-1α), and induces insulin resistance through SOCS3-mediated inhibition of insulin signaling. …

Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

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… Pharmacologically targeting fatty acid synthase-mediated de novo lipogenesis alleviates osteolytic bone loss by directly inhibiting osteoclastogenesis through suppression of STAT3 palmitoylation and ROS signaling. Metabolism . 2025;167:156186. doi: 10.1016/j.metabol.2025.156186 62. …

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue wei

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… Studies on animal models showed that testosterone exposure and neonatal androgenization in female mice led to an increase in WAT with adipocyte hypertrophy, a decreased insulin-dependent lipogenesis, hypoadiponectinemia, and a decrease of the intensity of POMC neuronal projections within the arcuate …

Exploring COX-Independent Pathways: A Novel Approach for Meloxicam and Other NSAIDs in Cancer and Cardiovascular Disease Treatment.

As a fundamental process of innate immunity, inflammation is associated with the pathologic process of various diseases and constitutes a prevalent risk factor for both cancer and cardiovascular disease (CVD). Studies have indicated that several non-steroidal anti-inflammatory drugs (NSAIDs), including Meloxicam, may prevent tumorigenesis, reduce the risk of carcinogenesis, improve the efficacy of anticancer therapies, and reduce the risk of CVD, in addition to controlling the body's inflammatory imbalances. Traditionally, most NSAIDs work by inhibiting cyclooxygenase (COX) activity, thereby b

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… Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutant colorectal cancer. Redox Biol. 2022;55:102426. doi: 10.1016/j.redox.2022.102426. 36. Chen Z., Wang C., Dong H., Wang X., Gao F., Zhang S., Zhang X. …

Effects of glucocorticoid replacement therapy in patients with pituitary disease: A new perspective for personalized replacement therapy.

Secondary adrenal insufficiency (SAI) is an endocrine disorder due to impaired secretion of ACTH resulting from any disease affecting the pituitary gland. Glucocorticoid replacement therapy is mandatory to ensure patient survival, haemodynamic stability, and quality of life. In fact, a correct dose adjustement is mandatory due to the fact that inappropriately low doses expose patients to hypoadrenal crisis, while inappropriately high doses contribute to glucose metabolic and cardiovascular deterioration. This review analyses the current evidence from available publications on the epidemiology

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… Cortisol acts on adipose tissue, increasing lipolysis in subcutaneous tissue of the extremities and activating lipogenesis in visceral and subcutaneous adipose tissue of the trunk. In addition, cortisol alters insulin action leading to hyperglycemia [ 13 ] and it increases proteolysis [ 14 ]. …

Advances in delivery methods of Arthrospira platensis (spirulina) for enhanced therapeutic outcomes.

Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against

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… [ 76 ] that high levels of GIP inhibit the lipolysis and stimulate lipogenesis, eventually leading to obesity. The idea of inhibiting DPP-4 will help in not disturbing the incretins by lowering the blood glucose level. …

Defining neuroblastoma: From origin to precision medicine.

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation

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… Notably, MYCN upregulates enzymes participating in lipogenesis including fatty acid synthase (FASN) and acetyl-CoA carboxylase A (ACACA). …

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

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… The PTEN/PI3K/AKT axis regulates de novo lipogenesis by controlling sterol response element-binding protein (SREBP) expression and inhibiting the forkhead transcription factor FOXO1, which negatively regulates SREBP transcription and vice versa ( 80 , 81 ). …

PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be

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… Arginine Methylation of SREBP1a via PRMT5 Promotes De Novo Lipogenesis and Tumor Growth Cancer Res. 2016 76 1260 1272 10.1158/0008-5472.CAN-15-1766 26759235 81. Pal S. Vishwanath S.N. Erdjument-Bromage H. Tempst P. Sif S.D. …

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

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… Galectin-12 inhibits granulocytic differentiation of human NB4 promyelocytic leukemia cells while promoting lipogenesis. J. Leukoc. Biol. 2016;100:657–664. doi: 10.1189/jlb.1HI0316-134R. …

Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.

Cancer remains a major global health challenge, with therapeutic resistance significantly limiting treatment success. Traditional approaches, including surgery, chemotherapy, and radiotherapy, often encounter barriers such as metastasis and adverse effects on healthy tissues. The Warburg effect, which describes cancer cells’ reliance on glucose fermentation despite oxygen availability, has prompted investigations into alternative metabolic interventions. The ketogenic diet (KD), characterized by high fat intake and low carbohydrate intake, induces a metabolic shift that may selectively disadva

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… The protective effects of the KD appear to be mediated through metabolic reprogramming that reduces substrate availability for lipogenesis and inflammatory pathways, enhanced apoptotic regulation via caspase-3 activation and p21-mediated cell cycle arrest, and modulation of the tumor microenvironment …

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… Inhibition of HDAC 11 promotes the inhibition of lipogenesis and promotes fatty acid oxidation in the liver. Cyclic peptides [ 115 ] and hydroxamic acids (PB94) [ 116 ] have been studied as HDAC11 inhibitors ( Table 6 ). Table 6 Chemical structures of HDAC11 inhibitors. …

Complement C3a promotes the formation of osteoclasts by inhibiting Sirt1 to activate the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

BACKGROUND: Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the complement C3a activates osteoclasts to participate in the pathogenesis of MBD; however, its mechanism of action is diverse and complex. Studies have shown that the Sirtuin (Sirt) family of proteins (i.e., Sirt1-7) are expressed in human bone and cartilage, and participate in bone metabolic balance. METHODS AND RESULTS: We measured the levels of complement C3a, Sirt1, osteoclast-related genes, and bone disease-related biological indicators using enzyme-linked imm

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… Gly-tRFs promote lipogenesis and inhibit fatty-acid β-oxidation by regulating the Sirt1 signaling pathway in alcoholic fatty liver disease (AFLD), which reveals an interaction between C3a and Sirt1. …

DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.

As an important nutrient in the human body, cholesterol can not only provide structural components for the body's cells, but also can be transformed into a variety of active substances to regulate cell signaling pathways. As an important cholesterol synthase, DHCR24 participates in important regulatory processes in the body. The application of DHCR24 in tumor clinical diagnosis and treatment also attracts much attention. This article reviews the structure and regulatory characteristics of DHCR24, and the research of DHCR24 on tumor progression. We summarize the possible mechanisms of DHCR24 pr

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… The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis. Nature. 2020;580(7804):530-535. doi: 10.1038/s41586-020-2183-2 48. Bae SH, Paik YK. …

Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underl

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… Lipid desaturation—the next step in targeting lipogenesis in cancer? FEBS J. 2016 283 2767 2778 10.1111/febs.13681 26881388 70. Gottgens E.L. van den Heuvel C.N. de Jong M.C. Kaanders J.H. Leenders W.P. Ansems M. Bussink J. Span P.N. …

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

PROTAC Technology as a New Tool for Modern Pharmacotherapy.

The publication focuses on the innovative applications of PROTAC (proteolysis-targeting chimera) technology in modern pharmacotherapy, with particular emphasis on cancer treatment. PROTACs represent an advanced therapeutic strategy that enables selective protein degradation, opening new possibilities in drug design. This technology shows potential in the treatment of cancers, viral infections (such as HIV and COVID-19), and chronic diseases including atherosclerosis, Alzheimer's disease, atopic dermatitis, and Huntington's disease. Promising results from clinical studies on the compound ARV-47

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… Degradation of SREBP by PROTACs can lead to reduced lipogenesis in the liver, which is essential for treating NAFLD. SREBPs are key transcription factors regulating genes involved in cholesterol, fatty acid, and triglyceride biosynthesis. …

The role of abnormal epigenetic regulation of small GTPases in glioma (Review).

Brain tumors are one of the most severe types of malignant tumors and glioma accounts for ~80% of malignant brain tumors. The current treatment methods for glioma are limited and patients with glioma often experience relapse following treatment, which leads to a poor prognosis for these patients. Therefore, novel therapeutic targets and methods urgently need to be explored. The present review screened studies that mainly focused on the epigenetic regulation of small guanosine triphosphate (GTP)ase in glioma. These small GTPases participate in most cellular biological processes, including diffe

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… Rab27B in human breast cancer correlates closely with lymph node metastasis and predicts poor prognosis J Transl Med 10 242 2012 10.1186/1479-5876-10-242 23217148 PMC3539959 32 You X Liu F Zhang T Li Y Ye L Zhang X Hepatitis B virus X protein upregulates oncogene Rab18 to result in the dysregulation of lipogenesis …

The "Road" to Malignant Transformation from Endometriosis to Endometriosis-Associated Ovarian Cancers (EAOCs): An mTOR-Centred Review.

Ovarian cancer is an umbrella term covering a number of distinct subtypes. Endometrioid and clear-cell ovarian carcinoma are endometriosis-associated ovarian cancers (EAOCs) frequently arising from ectopic endometrium in the ovary. The mechanistic target of rapamycin (mTOR) is a crucial regulator of cellular homeostasis and is dysregulated in both endometriosis and endometriosis-associated ovarian cancer, potentially favouring carcinogenesis across a spectrum from benign disease with cancer-like characteristics, through an atypical phase, to frank malignancy. In this review, we focus on mTOR d

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… The de novo lipogenesis is mainly regulated at the transcriptional level by activating regulatory element-binding proteins (SREBPs). …

Current Advancement of Immunomodulatory Drugs as Potential Pharmacotherapies for Autoimmunity Based Neurological Diseases.

Dramatic advancement has been made in recent decades to understand the basis of autoimmunity-mediated neurological diseases. These diseases create a strong influence on the central nervous system (CNS) and the peripheral nervous system (PNS), leading to various clinical manifestations and numerous symptoms. Multiple sclerosis (MS) is the most prevalent autoimmune neurological disease while NMO spectrum disorder (NMOSD) is less common. Furthermore, evidence supports the presence of autoimmune mechanisms contributing to the pathogenesis of amyotrophic lateral sclerosis (ALS), which is a neurodeg

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… Moreover, the microbiota can communicate with host physiology, i.e., lipogenesis, apoptosis, insulin control, and hormonal and neuronal signaling through the production of secondary metabolites. Figure 4 Gut–brain axis. …