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Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.

The need for new, more effective drugs to treat cancer, infectious diseases, various parasitic infestations, and metabolic disorders requires innovative approaches to the design of promising molecules. One of these areas is the creation of hybrid structures. Lupane triterpenoids are of significant interest for such research due to their high abundance in natural sources and their renewable nature, their molecular architecture, presence of several easily modifiable functional groups, enantiomeric purity, broad spectrum of biological activity, and low toxicity. Active research into the biologica

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… Notably, this compound has been shown to modulate adipogenesis by reducing both gene and PPAR-gamma protein expression, as well as regulating co-factor specificity [ 158 ]. Figure 39 PPARγ antagonists from lupane series. …

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

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… Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated Nutrients 2023 15 5082 10.3390/nu15245082 38140341 PMC10745682 43. King J.S. Veltman D.M. Insall R.H. …

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing seve

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… TNF-α, NF-κB, RUNX-2, collagen X, β-catenin | [ 196 ] | In vivo | 10 mg/kg | OA-induced mice model | ↓OARSI score | [ 196 ] | In vitro | 2–128 μM | Chondrocytes | ↓NOS, cox-2, MMP-3, MMP-13, ERK1/2, PI3K/Akt | [ 72 ] Obesity | In vitro | 25, 50, 75 μM | 3T3-L1 pre-adipocytes | ↓Lipid accumulation, adipogenesis …

Close interactions between lncRNAs, lipid metabolism and ferroptosis in cancer.

Abnormal lipid metabolism including synthesis, uptake, modification, degradation and transport has been considered a hallmark of malignant tumors and contributes to the supply of substances and energy for rapid cell growth. Meanwhile, abnormal lipid metabolism is also associated with lipid peroxidation, which plays an important role in a newly discovered type of regulated cell death termed ferroptosis. Long noncoding RNAs (lncRNAs) have been proven to be associated with the occurrence and progression of cancer. Growing evidence indicates that lncRNAs are key regulators of abnormal lipid metabo

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… Moreover, the reduction in pancreatic cancer cell adipogenesis after inhibiting the expression of SREBP2 further proves that lncRNA SNHG16 may fuel the growth of pancreatic cancer cells by regulating the miR-195/SREBP2 axis to provide an energy supply 45 . …

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A m

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

Sending the Signal to Bone: How Tumor-Derived EVs Orchestrate Pre-Metastatic Niche Formation and Skeletal Colonization.

Bone is a preferred site for disseminated tumor cells, yet the molecular mechanisms that prepare the skeletal microenvironment for metastatic colonization are only beginning to be understood. At the heart of this process are extracellular vesicles (EVs), nano-sized, lipid-encapsulated particles secreted by cancer cells and stromal components. This review consolidates current findings that position EVs as key architects of the bone-metastatic niche. We detail the biogenesis of EVs and their organotropic distribution, focusing on how integrin patterns and bone-specific ligands guide vesicle homi

An overview of multiple myeloma: A monoclonal plasma cell malignancy's diagnosis, management, and treatment modalities.

Multiple Myeloma (MM) is a plasma cell cancer with high mortality and morbidity rates. Its incidence rate has increased by 143% since 1975. Adipokines, cytokines, chemokines, and genetic variations influence the development and progression of MM. Chromosomal translocations cause mutations associated with MM. The pathogenesis of MM is complicated by novel issues like miRNAs, RANKL, Wnt/DKK1, Wnt, and OPG. Conventional diagnosis methods include bone marrow biopsy, sPEP or uPEP, sIFE and uIFE, and sFLC assay, along with advanced techniques such as FISH, SNPA, and gene expression technologies. A n

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… Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance. Inflammation. 2022;45(1):31–44. doi: 10.1007/s10753-021-01559-z. …

Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK c

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… Multiple Myeloma Cells Alter Adipogenesis, Increase Senescence-Related and Inflammatory Gene Transcript Expression, and Alter Metabolism in Preadipocytes. Front Oncol (2021) 10:584683. doi: 10.3389/fonc.2020.584683 115. Adamik J, Galson DL, Roodman GD. …

Polyphenols: Chemoprevention and therapeutic potentials in hematological malignancies.

Polyphenols are one of the largest plant-derived natural product and they play an important role in plants' defense as well as in human health and disease. A number of them are pleiotropic molecules and have been shown to regulate signaling pathways, immune response and cell growth and proliferation which all play a role in cancer development. Hematological malignancies on the other hand, are cancers of the blood. While current therapies are efficacious, they are usually expensive and with unwanted side effects. Thus, the search for newer less toxic agents. Polyphenols have been reported to po

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… Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells. J Physiol Biochem. (2019) 75:83–8. 10.1007/s13105-018-0659-4 48. Yen SC, Chen LC, Huang HL, Ngo ST, Wu YW, Lin TE, et al. …

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy.

The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogram

NAD+‒circadian rhythm coupling in dementia.

The circadian rhythm system and sleep coordinate whole-body functions across the 24-h cycle, yet these rhythms progressively deteriorate with neurodegenerative diseases, including dementia. Growing evidence indicates that nicotinamide adenine dinucleotide (NAD+) interacts with the circadian system through multiple molecular pathways and that NAD+ levels decline with dementia. In this review, we synthesize current evidence on the bidirectional relationship between NAD+ metabolism and circadian regulation in several dementia disorders, emphasizing the key circadian pathways, the nicotinamide pho

Unlocking the therapeutic potential of cellular mechanobiology.

Mechanobiology is a rapidly advancing field at the intersection of biology, physics, and engineering that reveals how mechanical forces shape cellular behavior, tissue architecture, and disease progression. By elucidating how cells sense and transduce mechanical cues, mechanobiology has fundamentally advanced our understanding of processes ranging from migration and differentiation to immune responses and tissue remodeling. These advances have driven the development of innovative biophysical tools and engineered biomaterials that enable precise modulation of the cellular microenvironment. Tran

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… Nonetheless, curvature-driven mechanical gradients have been shown to regulate cell fate decisions, promoting osteogenesis on convex zones and adipogenesis in concave regions ( 45 , 46 ). …

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

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… Cbfβ governs osteoblast− adipocyte lineage commitment through enhancing β-catenin signaling and suppressing adipogenesis gene expression. Proc Natl Acad Sci. 2017;114(38):10119–24. 44. Azadniv M, Myers JR, McMurray HR, Guo N, Rock P, Coppage ML, et al. …

Navigating the Landscape of Exosomal microRNAs: Charting Their Pivotal Role as Biomarkers in Hematological Malignancies.

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically

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… They also impair osteoblast differentiation, shifting bone marrow mesenchymal progenitors away from osteogenesis toward adipogenesis, a lineage switch contributing to bone loss and niche dysfunction [ 162 ]. 4.2.4. …

Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med

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… Prostate | miR-196a | miRNA | 89 | 100 | ( 147 , 149 ) Prostate | lincRNA-p21 | lincRNA | 67 | 63 | ( 147 , 150 ) Prostate | lincRNA-p21/PSA | lincRNA | 53 | 94 | ( 147 , 150 ) Prostate | miR-1246 | miRNA | 75 | 100 | ( 151 ) Prostate | Transmembrane protein 256 | Protein | 94 | 100 | ( 151 ) Prostate | Adipogenesis …

Recent Review on Biological Barriers and Host-Material Interfaces in Precision Drug Delivery: Advancement in Biomaterial Engineering for Better Treatment Therapies.

Preclinical and clinical studies have demonstrated that precision therapy has a broad variety of treatment applications, making it an interesting research topic with exciting potential in numerous sectors. However, major obstacles, such as inefficient and unsafe delivery systems and severe side effects, have impeded the widespread use of precision medicine. The purpose of drug delivery systems (DDSs) is to regulate the time and place of drug release and action. They aid in enhancing the equilibrium between medicinal efficacy on target and hazardous side effects off target. One promising approa

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… Human mesenchymal stem cells (MSCs) can be easily redirected from adipogenesis to osteogenesis by increasing the rate at which stress stiffening occurs in soft responsive hydrogels derived from synthetic polymers. …

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures.

The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age

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… Liu S Yang R Yin N Wang YL Faiola F Environmental and human relevant PFOS and PFOA doses alter human mesenchymal stem cell self-renewal, adipogenesis and osteogenesis Ecotoxicol Environ Saf 2019 169 564 572 10.1016/j.ecoenv.2018.11.064 30476818 170. …

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi

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… FFA, free fatty acid; TG, triglycerides Peroxisome proliferator-activated receptors (PPARs) signaling pathway PPARs are the nuclear receptors dependent on ligand binding 214 and activate targeted genes related to lipid and glucose metabolism and adipogenesis 215 , 216 . …

Natural biomolecules and derivatives as anticancer immunomodulatory agents.

Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remode

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… Notably, it inhibited adipogenesis and homing of triple-negative breast cancer cells ( 251 ). EGCG also synergized with curcumin to reduce tumor-supportive endothelial transition. …