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Low back pain caused by intervertebral disc degeneration (IDD) has emerged as a significant global public health concern, with far-reaching consequences for patients' quality of life and healthcare systems. Although previous research have revealed that the mechanisms of intervertebral disc cell apoptosis, pyroptosis and necroptosis can aggravate IDD damage by mediating inflammation and promoting extracellular matrix degradation, but they cannot explain the connection between different cell death mechanisms and ion metabolism disorders. The latest study shows that cell death mechanisms such as cellular senescence, ferroptosis, and cuproptosis, and PANopotosis have similar roles in the progression of intervertebral disc degeneration, but not exactly the same damage mechanism. This paper summarizes the effects of various cell death patterns on the disease progression of IDD, related molecular mechanisms and signaling pathways, providing new perspectives and potential clinical intervention strategies for the prevention and treatment of IDD. [ABSTRACT FROM AUTHOR]

Sepsis is described as a life-threatening organ dysfunction and a heterogeneous syndrome that is a leading cause of morbidity and mortality in intensive care settings. Severe sepsis could incite an uncontrollable surge of inflammatory cytokines, and the host immune system's immunosuppression could respond to counter excessive inflammatory responses, characterized by the accumulated anti-inflammatory cytokines, impaired function of immune cells, overproliferation of myeloid-derived suppressor cells and regulatory T cells, depletion of immune effector cells by different means of death, etc. In this review, we delve into the underlying pathological mechanisms of sepsis, emphasizing both the hyperinflammatory phase and the associated immunosuppression. We offer an in-depth exploration of the critical mechanisms underlying sepsis, spanning from individual immune cells to a holistic organ perspective, and further down to the epigenetic and metabolic reprogramming. Furthermore, we outline the strengths of artificial intelligence in analyzing extensive datasets pertaining to septic patients, showcasing how classifiers trained on various clinical data sources can identify distinct sepsis phenotypes and thus to guide personalized therapy strategies for the management of sepsis. Additionally, we provide a comprehensive summary of recent, reliable biomarkers for hyperinflammatory and immunosuppressive states, facilitating more precise and expedited diagnosis of sepsis. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IVDD) is the pathological basis of disc herniation, spinal stenosis, and other related diseases, and the lower back pain it produces lays a heavy financial burden on individuals and society. Thus, it is essential to comprehend IVDD's pathophysiology. Numerous factors, such as inflammatory factors, oxidative stress, apoptosis, matrix metalloproteinases, are linked to IVDD pathogenesis. Despite the fact that many researches has provided explanations for the pathophysiology of IVDD, these studies are typically singular, restricted, and isolated, expound only on one or two components, and do not systematically analyze and summarize the numerous influencing elements. In addition, we discovered that the incidence of many chronic diseases in the field of orthopedics may be thoroughly and systematically defined in terms of immunological systems. In order to provide a theoretical foundation for an in‐depth understanding of the pathological process of IVDD and the formulation of more effective prevention and treatment measures, this review provides a comprehensive and systematic account of the pathogenesis of IVDD from the physical to the molecular barriers of the intervertebral disc, from the nucleus pulposus tissue to the cellular to the immune‐molecular level. [ABSTRACT FROM AUTHOR]

Abstract Intervertebral disc degeneration (IVDD) is the pathological basis of disc herniation, spinal stenosis, and other related diseases, and the lower back pain it produces lays a heavy financial burden on individuals and society. Thus, it is essential to comprehend IVDD's pathophysiology. Numerous factors, such as inflammatory factors, oxidative stress, apoptosis, matrix metalloproteinases, are linked to IVDD pathogenesis. Despite the fact that many researches has provided explanations for the pathophysiology of IVDD, these studies are typically singular, restricted, and isolated, expound only on one or two components, and do not systematically analyze and summarize the numerous influencing elements. In addition, we discovered that the incidence of many chronic diseases in the field of orthopedics may be thoroughly and systematically defined in terms of immunological systems. In order to provide a theoretical foundation for an in‐depth understanding of the pathological process of IVDD and the formulation of more effective prevention and treatment measures, this review provides a comprehensive and systematic account of the pathogenesis of IVDD from the physical to the molecular barriers of the intervertebral disc, from the nucleus pulposus tissue to the cellular to the immune‐molecular level.

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Developing biomaterial implants for bone regeneration usages has earned great attention during the last two decades. Doping technique is one of the recent approaches that have great promises in the enhancement of biomaterials features. Herein, the features of biphasic TCP/HA were modified by single and co-doping using silver (Ag+) and zirconium (Zr4+) on the expense of calcium utilizing chemical precipitation method. Doping effect on the physicochemical, thermal behaviour, particles charge, morphologies and mechanical properties was determined. Furthermore, dielectric, antibacterial activity, bioactivity and cell death mode (MG63 cell line) were also evaluated. It was confirmed that surface area and total pore volume of the prepared samples were improved upon doping. Negative particle charges, especially for the Zr4+ and the co-doped samples, were confirmed. The co-doped TCP/HA samples possess a strong bactericidal effect against all tested strains compared with the single-doped samples. They also showed a significant effect on the bioactivity properties and the electrical conductivity. The cell mode of death results also supports the importance of transition metal single and co-doping. Implementation of current co-doped biphasic calcium phosphate materials in bone reformation is encouraged due to their proved enhanced features. [ABSTRACT FROM AUTHOR]

Tissue-engineering has become the best alternative solution for replacing the damaged tissues. However, the cost of scaffold materials is still a big challenge, so the development of cost-effective scaffolds is highly encouraged. In this research, different types of cotton textile-scaffolds as a cellulosic material were developed to be utilized as a substrate for cells proliferation. They were loaded with bioactive glass (BG) doped with silver nanoparticles (AgNPs). The effect of the loaded materials on the physicochemical and mechanical characteristics of the cellulosic textile scaffolds was investigated by means of FTIR, contact angle, physical and mechanical properties of the cotton fabrics, in addition to assessing their antimicrobial activity. Moreover, the biomineralization was evaluated after soaking in Simulated Body Fluid (SBF) using ICP and SEM accessorized with EDX. Cells proliferation capacities of the developed cellulosic woven-scaffolds were assessed against MG63 cell line at different incubation times. The physicochemical and mechanical features of these fabrics demonstrated a positive influence for the existence of BG impregnation, especially those doped with AgNPs. The antimicrobial features were also affirmed for the cellulosic scaffolds. More pronounced influence was observed on the biomineralization of the scaffold impregnated with BG doped with 0.5% Ag. The percentages of proliferated cells were very close to negative control (100% ± 10). This approach offers a novel and affordable alternative cellulosic woven-scaffolds for bone regeneration. • Affordable cotton textile scaffolds were developed for bone regeneration. • Enhanced physicochemical and mechanical features by BG impregnations. • Antibacterial, bioactivity and cell proliferation are achieved. [ABSTRACT FROM AUTHOR]

Great attention has been bestowed upon iridium(III) complexes as anticancer agents in recent years, and a variety of them, in particular, are luminescent. The phosphorescence of these compounds facilitates the visualization and monitoring of their subcellular localization and interactions with other molecules or structures during anticancer therapy, which might help demonstrate the inner pathways and molecular mechanisms of the complexes. In this review, we focus on the development of phosphorescent iridium(III) complexes for anticancer applications in recent five years and intend to highlight some newly reported Ir(III) complexes that are targeting specific organelles, inducing different cell death modes, or photoactivated agents in phototherapies including photodynamic therapy and photoredox catalysis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a frequent chronic joint disease in orthopedics that effects individuals and society significantly. Obesity, aging, genetic susceptibility, and joint misalignment are all known risk factors for OA, but its pathomechanism is still poorly understood. Researches have revealed that OA is a much complex process related to inflammation, metabolic and chondrocyte death. It can affect all parts of the joint and is characterized by causing chondrocyte death and extracellular matrix descent. Previously, OA was thought to develop from excessive mechanical loading leading to the destruction of articular cartilage. Since some programmed cell deaths and OA share a pattern of chondrocyte destruction, it is likely that OA also involves programmed cell death. Even though chondrocyte apoptosis and pyroptosis have been investigated in OA, clarifing solely conventional cell death pathways is still insufficient to understand the pathophysiology of osteoarthritis. With more researches, it has been discovered that osteoarthritis and other new cell death processes, including PANoptosis, ferroptosis, and cell senescence, are strongly associated. Among these, PANoptosis combines the key traits of pyroptosis, cell apoptosis, and necrotic apoptosis into a highly coordinated and dynamically balanced programmed inflammatory cell death mechanism. Furthermore, we think that PANopotosis might obstruct necroptosis and cell senescence. Therefore, in order to offer direction for therapeutic treatment, we evaluate the development of research on multiple cell death of chondrocytes in OA. [Display omitted] • In osteoarthritis, inflammatory mediators such as ROS, IL, NO, and MMP are closely related to chondrocyte apoptosis. • Ferroptosis regulates articular chondrocyte and matrix homeostasis by interacting with lipid peroxidation, oxidative stress, and inflammatory responses, resulting in synovitis, articular cartilage degeneration. • PANoptosis is a highly coordinated and dynamically balanced programmed inflammatory cell death pathway that combines the key features of pyroptosis, apoptosis, and necroptosis. [ABSTRACT FROM AUTHOR]

Artemisinin, a natural allelochemical substance extracted from Artemisia annua , has been shown to have strong inhibitory effects on harmful cyanobacteria. However, only a few studies have systematically studied the mechanism of artemisinin in inhibiting algae and the process of algae cell death. In this study, the inhibition mechanism and death mode of M. aeruginosa under artemisinin sustained-release microspheres (ASMs) were investigated using a series of morphological, physiological and biochemical characteristics. The findings revealed that M. aeruginosa was significantly inhibited immediately after exposure to the 0.54 g·L−1 ASMs, with an inhibition rate (IR) exceeding 95 %, and the synthesis of phycobiliprotein and esterase activity were disturbed. In addition, ASMs exposure significantly increased caspase-3(-like) activities of M. aeruginosa. Under the continuous stress of ASMs, M. aeruginosa cells had three cell death modes: the first was necrosis-like cell death, which was characterized by cell wall rupture and leakage of cell contents; the second was apoptosis-like cell death, which was characterized by the disintegration of the cell structure, the integrity of the cell membrane, and the appearance of apoptotic bodies; and the last was autophagy-like cell death, which was characterized by cell swelling and appearance of autophagy vacuoles. These results indicated that ASMs could inhibit photosynthesis of M. aeruginosa cells, interfere with its antioxidant mechanisms and activate caspase-3(-like) activity, resulting in programmed cell death (PCD). [Display omitted] • Artemisinin sustained-release microspheres (ASMs) could inhibit M. aeruginosa significantly. • ASMs interfered phycobiliprotein synthesis and esterase activity in M. aeruginosa. • Cells had three death modes: necrotic-like, apoptosis-like and autophagy-like. • PCD induced by ASMs in M. aeruginosa was caspase-3(−like) dependent. [ABSTRACT FROM AUTHOR]

The study was aimed at describing the mode of action of an innovative drug-like congener of fused azaisocytosine-EIMTC (ethyl 8-(4-methoxyphenyl)-4-oxo-6,7-dihydroimidazo[2,1- c][1,2,4]triazine-3-carboxylate)-on cancer cells in early in vitro oncology-related bioassays. Micromolar concentrations of EIMTC were effective at inhibiting the growth of two types of malignant multiple myeloma cells (including cells resistant to thalidomide) while having less cytotoxic effect on normal HSF cells. Furthermore, EIMTC was disclosed as capable of producing the statistically significant decrease in the number of cells in the S phase (in HeLa, TOV112D, T47D and Vero cells) and in the G/M phase (in TOV112D cells) as well as evoking the distinctly higher necrosis rates in malignant than normal cells of the same epithelial origin. These results are promising in the sense that the bicyclic nucleobase-like structure related to azaisocytosine may target epithelial cancer cells and inhibit their growth while having less effect on normal cells. This may be due to induction of necrosis. [ABSTRACT FROM AUTHOR]

Abstract: The interaction between ultrasound pulses and microbubbles is known to generate acoustic cavitation that may puncture biological cells. This work presents new experimental findings on the bioeffects of ultrasound-microbubble mediated cavitation in plant cells with emphasis on direct observations of morphological impact and analysis of viability trends in tobacco BY-2 cells that are widely studied in higher plant physiology. The tobacco cell suspensions were exposed to 1 MHz ultrasound pulses in the presence of 1% v/v microbubbles (10% duty cycle; 1 kHz pulse repetition frequency; 70 mm between probe and cells; 1-min exposure time). Few bioeffects were observed at low peak negative pressures (<0.4 MPa) where stable cavitation presumably occurred. In contrast, at 0.9 MPa peak negative pressure (with more inertial cavitation activities according to our passive cavitation detection results), random pores were found on tobacco cell wall (observed via scanning electron microscopy) and enhanced exogenous uptake into the cytoplasm was evident (noted in our fluorescein isothiocyanate dextran uptake analysis). Also, instant lysis was observed in 23.4% of cells (found using trypan blue staining) and programmed cell death was seen in 23.3% of population after 12 h (determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]). These bioeffects generally correspond in trend with those for mammalian cells. This raises the possibility of developing ultrasound-microbubble mediated cavitation into a targeted gene transfection paradigm for plant cells and, conversely, adopting plant cells as experimental test-beds for sonoporation-based gene therapy in mammalian cells. [Copyright &y& Elsevier]

Abstract: Apoptosis is induced not only during morphogenesis and embryogenesis but also under various pathological conditions, especially related to oxidative stress. Apoptotic cells are phagocytized by neighboring cells while necrotic cells cause local and general reactions sometimes lethal to our bodies. Data have been accumulated to demonstrate that the switch of the cell death mode from apoptosis to necrosis does occur. However, detailed mechanisms involved in the switch mechanism remain unsolved although decreases in the intracellular level of ATP and a burst in the cellular level of reactive oxygen species (ROS) have been proposed. Recently, we have shown that the population of apoptotic cells reaches maximum in human osteosarcoma 143B cells treated for 6h with menadione (MEN) while necrotic cells become predominant at 9h of the treatment. In the present study we have attempted to clarify the role of cellular ATP in the switch mechanism using ρ 0 cells derived from human osteosarcoma ρ + cells. Results are summarized as follows: (1) Apoptotic and necrotic changes in ρ 0 cells are much faster than ρ + cells after the treatment with MEN. (2) Cellular level of ATP in ρ 0 cells remains essentially in the same level before and after the MEN-treatment while intracellular levels of superoxide continuously increase after the MEN-treatment. (3) ρ + cells treated with MEN in the presence of antimycin A plus oligomycin show similar changes to those of MEN-treated ρ 0 cells. (4) MEN-induced increases in the cellular level of superoxide are distinctly suppressed by inhibitors of NADPH oxidase. These results suggest that the intracellular level of superoxide may be a key factor directly related to the switch mechanism from apoptosis to necrosis, and that decreases in cellular level of ATP accelerate both apoptotic and necrotic changes of the cells. [Copyright &y& Elsevier]

Background/aim: We previously showed that oxaliplatin induces necrotic-like cell death in hepatocarcinomas, and combination with ursodexoycholic acid (UDCA) significantly shifts the necrotic-like death to apoptosis. Since cell death mode is crucial on inflammatory responses and chemotherapeutic efficacy, the mechanism underlying determination of cell death mode by UDCA was investigated in this study., Materials and Methods: Apoptosis or necrosis was determined by apoptotic body formation, caspase-8 activity, LDH release and PI inclusion. The involvement of lipid rafts and death receptors was examined by rafts fractionation, confocal microscopy and gene silencing assays., Results: UDCA combination enhanced recruitment of death receptors and adaptors into cholesterol-enriched lipid rafts, and induced a stronger raft clustering. Lipid raft disruption decreased the UDCA/oxaliplatin-mediated apoptosis and increased necrotic-like death., Conclusion: UDCA promotes lipid raft localization of multiple death receptors, thereby contributing to a shift of cell death mode from oxaliplatin-induced necrotic death to apoptosis in HepG2 cells., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)