Despite affecting approximately 30% of the population, the pathogenesis of temporomandibular disorders (TMD) remains poorly understood. Conditions such as disc displacement and joint degeneration are often associated with biomechanical dysfunction. Identifying and categorizing biomarkers in the articular disc may enhance our understanding of disease mechanisms and progression, potentially improving diagnostic accuracy and therapeutic outcomes. This review examines patterns among immunohistochemical biomarkers in the articular disc, with a focus on internal derangement and disc displacement. It also explores associations with clinical, radiological, and histological findings, defining the functional and stage-specific relevance of each marker. A systematic search of major databases and journals identified studies that used immunohistochemical methods and included control groups. Biomarker patterns were analyzed in isolation and in relation to clinical, radiological, and histological findings. Patient demographics were examined to determine their alignment with disease trends. Study selection followed PRISMA guidelines; bias was assessed using the Newcastle-Ottawa Scale. The review included 511 patients (579 samples) and 132 controls (158 samples). Analysis identified 24 biomarkers, providing valuable insights into their role in inflammatory progression, ECM remodeling, and tissue degeneration. Biomarkers were classified according to functional and stage-specific patterns, facilitating early detection, refining disease staging, and supporting individualized treatment strategies. Disc biopsy offers unique insights into the joint- and disc-specific mechanisms that drive TMD progression from disc displacement to degenerative findings. However, its clinical use remains limited by its invasive nature, ethical constraints, and the lack of standardized protocols for reliable study design and validated biomarker profiles.

Cancer Stem Cells (CSCs) represent a heterogeneous group of tumor cells that possess the innate ability to self-renew and differentiate, which also contributes to their resistance to first-line therapies. What sets CSCs apart from others is their crucial role in the recurrence of cancer, metastasis, and varied clinical responses against anti-cancer drugs, which makes them challenging to target. In recent years, there has been growing evidence that therapies capable of eliminating CSC niches or specifically targeting their core survival mechanisms are a potential means of providing a sustainable, long-term response to therapy and increasing disease-free survival rates. Bioactive compounds from natural sources have gained immense interest for their bio-efficacy, low toxicity profiles, and wide therapeutic index (TI), especially with their broad-spectrum ability of targeting multiple pathways while having little or no systemic side effects. Bioactive compounds can target major signaling pathways (Wnt/β-catenin, Notch, Hippo-YAP/TAZ, Hedgehog, PI3K/Akt/mTOR, NF-κB) to induce apoptosis, inhibit epithelial-mesenchymal transition (EMT), disrupt cancer stem cell niches, and other effects that suggest they resensitize to chemotherapeutic agents. Plant-derived biologics may be used as unique strategies targeting CSCs or as adjuncts reconstituted with custom conventional treatment plans, to mitigate drug resistance with mechanisms that involve targeting CSC metabolism, blocking protective autophagy, and the epigenetic landscape. The use of nanotechnology for targeted delivery of bioactive compounds is anticipated to provide better stability, bioavailability, and tumor accumulation. In this review, we outline a range of approaches using bioactive compounds for the eradication of CSCs, focusing on the mechanisms by which they work, the preclinical and clinical evidence supporting them, and their role in combination therapy approaches. This review also gives a comprehensive understanding of various other strategies and latest advancements that do not directly target the CSCs, including differentiation therapy, metabolic targeting, and immunomodulation, which, when used in conjunction with bioactive compounds, may resensitize the drug-resistant CSC population. We also discuss the therapeutic and translational potential of bioactive compounds and the future possibilities of combination, multi-targeted, CSC-based treatment strategies to eliminate tumor recurrences and improve cancer outcomes for patients.

Investigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.

Regenerative medicine promises the possibility of custom-made, ready-to-use human organs without the risk of immune rejection. Human pluripotent stem cells (hPSCs) are the workhorses of stem cell-based tissue engineering. With inherent capabilities to adopt nearly any cellular form, they are supposed to solve the soaring demand for transplantable organs. Technically, PSCs are converted into cells of interest using a stepwise approach (differentiation) mimicking embryonic development. Animal models have been crucial in advancing our understanding of human embryology, mainly due to the widespread conservation of the mammalian regulome. Differentiation protocols have evolved with time from two-dimensional (2D) monocultures, which are relatively easy to maintain, to more complex three-dimensional (3D) organoids that enhance the capacity for staging multilineage assemblies. The appeal of 3D systems lies in their operational resemblance to the actual morphology of tissues. While each platform has pros and cons, its specific strengths can be leveraged to tell a more compelling story of development and how complex pathologies take root. Here, we reviewed key methodologies for the in vitro production of human functional cell lineages from hPSCs. We have connected the most recent science to the work that came before and analyzed where the trends we see now might lead. We examined the shift from 2D cell monolayers to 3D organoids. Additionally, we highlighted hybrid approaches and innovative discoveries that support the reliable generation of physiologically mature cells, enabling the study of development and disease at new depths.