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Polymers Aug 2023The field of dental materials is undergoing rapid advancements in the pursuit of an innovative generation of dental polymeric restorative materials. There is a growing... (Review)
Review
The field of dental materials is undergoing rapid advancements in the pursuit of an innovative generation of dental polymeric restorative materials. There is a growing interest in the development of a distinct category of dental polymers that transcend the conventional role of inertly filling prepared cavities. Instead, these materials possess the capacity to actively detect and respond to alterations within the host environment by undergoing dynamic and controlled molecular changes. Despite the well-established status of stimuli-responsive polymeric systems in other fields, their implementation in dentistry is still in its nascent stages, presenting a multitude of promising opportunities for advancement. These systems revolve around the fundamental concept of harnessing distinctive stimuli inherent in the oral environment to trigger precise, targeted, predictable, and demand-driven responses through molecular modifications within the polymeric network. This review aims to provide a comprehensive overview of the diverse categories of stimuli-responsive polymers, accentuating the critical aspects that must be considered during their design and development phases. Furthermore, it evaluates their current application in the dental field while exploring potential alternatives for future advancements.
PubMed: 37631403
DOI: 10.3390/polym15163346 -
Frontiers in Oncology 2023The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by... (Review)
Review
The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by inducing immunogenic cell death and durably eradicate tumors. This suggests that immunogenic chemotherapy holds great potential for improving response rates. However, chemotherapy in practice has only had limited success in inducing long-term survival or cure of cancers when used either alone or in combination with immunotherapy. We think that this is because the importance of dose, schedule, and tumor model dependence of chemotherapy-activated anti-tumor immunity is under-appreciated. Here, we review immune modulation function of representative chemotherapy agents and propose a model of immunogenic chemotherapy-induced long-lasting responses that rely on synergetic interaction between killing tumor cells and inducing anti-tumor immunity. We comb through several chemotherapy treatment schedules, and identify the needs for chemotherapy dose and schedule optimization and combination therapy with immunotherapy when chemotherapy dosage or immune responsiveness is too low. We further review tumor cell intrinsic factors that affect the optimal chemotherapy dose and schedule. Lastly, we review the biomarkers indicating responsiveness to chemotherapy and/or immunotherapy treatments. A deep understanding of how chemotherapy activates anti-tumor immunity and how to monitor its responsiveness can lead to the development of more effective chemotherapy or chemo-immunotherapy, thereby improving the efficacy of cancer treatment.
PubMed: 38125944
DOI: 10.3389/fonc.2023.1308681 -
Plants (Basel, Switzerland) Nov 2023Rice ( L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in... (Review)
Review
Rice ( L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world's rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice's reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms.
PubMed: 38068585
DOI: 10.3390/plants12233948 -
Journal For Immunotherapy of Cancer Aug 2023Adjuvants are key for effective vaccination against cancer and chronic infectious diseases. Saponin-based adjuvants (SBAs) are unique among adjuvants in their ability to...
BACKGROUND
Adjuvants are key for effective vaccination against cancer and chronic infectious diseases. Saponin-based adjuvants (SBAs) are unique among adjuvants in their ability to induce robust cell-mediated immune responses in addition to antibody responses. Recent preclinical studies revealed that SBAs induced cross-presentation and lipid bodies in otherwise poorly cross-presenting CD11b murine dendritic cells (DCs).
METHOD
Here, we investigated the response of human DC subsets to SBAs with RNA sequencing and pathway analyses, lipid body induction visualized by laser scanning microscopy, antigen translocation to the cytosol, and antigen cross-presentation to CD8 T cells.
RESULTS
RNA sequencing of SBA-treated conventional type 1 DC (cDC1) and type 2 DC (cDC2) subsets uncovered that SBAs upregulated lipid-related pathways in CD11c CD1c cDC2s, especially in the CD5 CD163 CD14 cDC2 subset. Moreover, SBAs induced lipid bodies and enhanced endosomal antigen translocation into the cytosol in this particular cDC2 subset. Finally, SBAs enhanced cross-presentation only in cDC2s, which requires the CD163 CD14 cDC2 subset.
CONCLUSIONS
These data thus identify the CD163 CD14 cDC2 subset as the main SBA-responsive DC subset in humans and imply new strategies to optimize the application of saponin-based adjuvants in a potent cancer vaccine.
Topics: Humans; Animals; Mice; Cross-Priming; CD8-Positive T-Lymphocytes; Adjuvants, Immunologic; Dendritic Cells; Saponins
PubMed: 37612044
DOI: 10.1136/jitc-2023-007082 -
Scientific Reports Nov 2023Temperature is a primary factor affecting the physiology of ectothermic animals and global warming of water bodies may therefore impact aquatic life. Understanding the...
Temperature is a primary factor affecting the physiology of ectothermic animals and global warming of water bodies may therefore impact aquatic life. Understanding the effects of near-future predicted temperature changes on the behaviour and underlying molecular mechanisms of aquatic animals is of particular importance, since behaviour mediates survival. In this study, we investigate the effects of developmental temperature on locomotory behaviour and olfactory learning in the zebrafish, Danio rerio. We exposed zebrafish from embryonic stage to either control (28 °C) or elevated temperature (30 °C) for seven days. Overall, warming reduced routine swimming activity and caused upregulation of metabolism and neuron development genes. When exposed to olfactory cues, namely catfish cue, a non-alarming but novel odour, and conspecifics alarming cue, warming differently affected the larvae response to the two cues. An increase in locomotory activity and a large transcriptional reprogramming was observed at elevated temperature in response to novel odour, with upregulation of cell signalling, neuron development and neuron functioning genes. As this response was coupled with the downregulation of genes involved in protein translation and ATP metabolism, novel odour recognition in future-predicted thermal conditions would require energetic trade-offs between expensive baseline processes and responsive functions. To evaluate their learning abilities at both temperatures, larvae were conditioned with a mixture of conspecifics alarm cue and catfish cue. Regardless of temperature, no behavioural nor gene expression changes were detected, reinforcing our findings that warming mainly affects zebrafish molecular response to novel odours. Overall, our results show that future thermal conditions will likely impact developing stages, causing trade-offs following novel olfactory detection in the environment.
Topics: Animals; Zebrafish; Odorants; Larva; Swimming; Temperature; Fever
PubMed: 38030737
DOI: 10.1038/s41598-023-48287-y -
Current Research in Physiology 2024The autonomic nervous system (ANS) regulates involuntary bodily functions such as blood pressure, heart rate, breathing, and digestion, in addition to controlling... (Review)
Review
The autonomic nervous system (ANS) regulates involuntary bodily functions such as blood pressure, heart rate, breathing, and digestion, in addition to controlling motivation and behavior. In older adults, the ANS is dysregulated, which changes the ability of the ANS to respond to physiological signals, regulate cardiovascular autonomic functionality, diminish gastric motility, and exacerbate sleep problems. For example, a decrease in heart rate variability, or the variation in the interval between heartbeats, is one of the most well-known alterations in the ANS associated with health issues, including cardiovascular diseases and cognitive decline. The inability to perform fundamental activities of daily living and compromising the physiological reactivity or motivational responses of older adults to moving toward or away from specific environmental stimuli are significant negative consequences of chronic and geriatric conditions that pose grave threats to autonomy, health, and well-being. The most updated research has investigated the associations between the action responsiveness of older adults and the maintenance of their physiological and physical health or the development of mental and physical health problems. Once autonomic dysfunction may significantly influence the development of different age-related diseases, including ischemic stroke, cardiovascular disease, and autoimmune diseases, this review aimed to assess the relationship between aging and autonomic functions. The review explored how motivational responses, physiological reactivity, cognitive processes, and lifelong developmental changes associated with aging impact the ANS and contribute to the emergence of health problems.
PubMed: 38510918
DOI: 10.1016/j.crphys.2024.100123 -
PLoS Pathogens Jul 2023Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals....
Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.
Topics: Animals; Mice; Lipopolysaccharides; Lung; Macrophages, Alveolar; Toll-Like Receptor 4; Carboxylic Ester Hydrolases
PubMed: 37498977
DOI: 10.1371/journal.ppat.1011556 -
Frontiers in Plant Science 2023Low temperature stress significantly threatens crop productivity and economic sustainability. Plants counter this by deploying advanced molecular mechanisms to perceive... (Review)
Review
Low temperature stress significantly threatens crop productivity and economic sustainability. Plants counter this by deploying advanced molecular mechanisms to perceive and respond to cold stress. Transmembrane proteins initiate these responses, triggering a series of events involving secondary messengers such as calcium ions (Ca), reactive oxygen species (ROS), and inositol phosphates. Of these, calcium signaling is paramount, activating downstream phosphorylation cascades and the transcription of cold-responsive genes, including cold-regulated (COR) genes. This review focuses on how plants manage freeze-induced damage through dual strategies: cold tolerance and cold avoidance. Tolerance mechanisms involve acclimatization to decreasing temperatures, fostering gradual accumulation of cold resistance. In contrast, avoidance mechanisms rely on cryoprotectant molecules like potassium ions (K), proline, glycerol, and antifreeze proteins (AFPs). Cryoprotectants modulate intracellular solute concentration, lower the freezing point, inhibit ice formation, and preserve plasma membrane fluidity. Additionally, these molecules demonstrate antioxidant activity, scavenging ROS, preventing protein denaturation, and subsequently mitigating cellular damage. By forming extensive hydrogen bonds with water molecules, cryoprotectants also limit intercellular water movement, minimizing extracellular ice crystal formation, and cell dehydration. The deployment of cryoprotectants is a key adaptive strategy that bolsters plant resilience to cold stress and promotes survival in freezing environments. However, the specific physiological and molecular mechanisms underlying these protective effects remain insufficiently understood. Therefore, this review underscores the need for further research to elucidate these mechanisms and assess their potential impact on crop productivity and sustainability, contributing to the progressive discourse in plant biology and environmental science.
PubMed: 37649996
DOI: 10.3389/fpls.2023.1246093 -
Translational Cancer Research Oct 2023Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone....
BACKGROUND
Immunotherapy has had a high success rate in treating lung adenocarcinoma (LUAD) for several decades. However, many patients do not benefit from immunotherapy alone. Recent studies revealed that a combination of immunotherapy and radiotherapy (RT) stimulates a good systemic immune response to LUAD. However, clinical and experimental evidence suggest that RT may give rise to primary immunodeficiency, facilitating tumor immunity escape. Little is known about the molecular mechanisms whereby RT and stereotactic body radiotherapy (SBRT) influence tumor immunogenicity and the effectiveness of immunotherapy in patients with LUAD.
METHODS
We investigated molecular markers that predict response to combination of immunotherapy and SBRT in the treatment of LUAD using bioinformatics.
RESULTS
SBRT significantly upregulated the expression of , , , , and and significantly downregulated the expression of , , and . Among these genes, the expression of , , and was associated with responsiveness to immunotherapy after SBRT. However, only and expression were associated with an improved prognosis. Further analysis revealed that and expression increased responsiveness to immunotherapy by promoting M0 macrophage and memory B cell infiltration of LUAD tissues.
CONCLUSIONS
In patients with , and expression are potential markers of a favorable response to combined immunotherapy and RT.
PubMed: 37969379
DOI: 10.21037/tcr-23-968 -
Frontiers in Plant Science 2023NAC transcription factors are an important genes that regulate plant growth and development, and can regulate functions such as fruit ripening in plants. Based on genome...
NAC transcription factors are an important genes that regulate plant growth and development, and can regulate functions such as fruit ripening in plants. Based on genome data of , the gene family was identified and analyzed by bioinformatics methods. In this study, we identified 85 genes in genome, and systematically analyzed the gene family. We found that they were distributed unevenly in the nineteen chromosomes. The amino acid length of gene family () ranged from 80 to 1065, molecular weight ranged from 22.17 to 119.02 kD, and isoelectric point ranged from 4.61~9.26. Its promoter region contains multiple stress responsive elements, including light responsive, gibberellin-responsive, abscisic acid responsiveness, MeJA-responsiveness and drought-inducibility elements. Phylogenetic analysis indicates that the gene family is most closely related to and . Analysis of SSR loci indicates that the fraction of mononucleotide repeats was the largest, as was the frequency of A/T. Non-coding RNA analysis showed that these 85 genes contain 397 miRNAs. The collinearity analysis shows that 9 collinear locis were found on the chromosomes of with , and 75 collinear locis with QRT-PCR experiment under different salt concentration and temperature conditions verified the response mechanism of gene family under stress conditions. Most genes are sensitive to salt stress and temperature stress. The results of this study provide a reference for further understanding the function of gene in .
PubMed: 37670854
DOI: 10.3389/fpls.2023.1232804