[Advances in Molecular Regulatory Mechanisms of Jaw Repair and Reconstruction]. / é¢Œéª¨ä¿®å¤é‡å»ºçš„åˆ†å­è°ƒæŽ§æœºåˆ¶ç ”ç©¶è¿›å±•.

Jawbone injuries resulting from trauma, diseases, and surgical resections are commonly seen in clinical practice, necessitating precise and effective strategies for repair and reconstruction to restore both function and aesthetics. The precise and effective repair and the reconstruction of jawbone injuries pose a significant challenge in the field of oral and maxillofacial surgery, owing to the unique biomechanical characteristics and physiological functions of the jawbone. The natural repair process following jawbone injuries involves stages such as hematoma formation, inflammatory response, ossification, and bone remodeling. Bone morphogenetic proteins (BMPs), transforming growth factor beta (TGF-ß), vascular endothelial growth factor (VEGF), and other growth factors play crucial roles in promoting jawbone regeneration. Cytokines such as interleukins and tumor necrosis factor play dual roles in regulating inflammatory response and bone repair. In recent years, significant progress in molecular biology research has been made in the field of jawbone repair and reconstruction. Tissue engineering technologies, including stem cell therapy, bioactive scaffolds, and growth factor delivery systems, have found important applications in jawbone repair. However, the intricate molecular regulatory mechanisms involved in the complex jawbone repair and reconstruction methods are not fully understood and still require further research. Future research directions will be focused on the precise control of these molecular processes and the development of more efficient combination therapeutic strategies to promote the effective and functional reconstruction of the jawbone. This review aims to examine the latest findings on the molecular regulatory mechanisms of the repair and reconstruction of jawbone injuries and the therapeutic strategies. The conclusions drawn in this article provide a molecular-level understanding of the repair of jawbone injuries and highlight potential directions for future research.

Runx1 alleviates osteoarthritis progression in aging mice.

With rates growing quickly with age, osteoarthritis (OA) is the most common cause of chronic disability in aging persons. The discomfort and reduced motion associated with osteoarthritis have a significant impact on quality of life, and there is no known solution. Runt-related transcription factor 1(Runx1) has been shown to play a protective role in the development of osteoarthritis by promoting chondrogenesis. We had created models of ageing mice with osteoarthritis by anterior cruciate ligament transection (ACLT) and analyzed the effects of intra-articular injection of adeno-associated virus/Runx1 (AAV/Runx1) on the models. The results showed that the AAV/Runx1-group maintained better articular cartilage integrity and retained more proteoglycan than the OA group after injection of AAV-Runx1. The markers related to pathological changes in cartilage were downregulated, while the markers related to physiological changes in cartilage were upregulated. This suggests that Runx1 may impede OA progression on the knee joint of ageing mice, potentially playing a protective role in OA and becoming a probable treatment target for osteoarthritis among ageing patients in the future.

TGF-ß3 mediates mitochondrial dynamics through the p-Smad3/AMPK pathway.

It is well recognized that mitochondrial dynamics plays a vital role in cartilage physiology. Any perturbation in mitochondrial dynamics could cause disorders in cartilage metabolism and even lead to the occurrence of cartilage diseases such as osteoarthritis (OA). TGF-ß3, as an important growth factor that appears in the joints of OA disease, shows its great potential in chondrocyte growth and metabolism. Nevertheless, the role of TGF-ß3 on mitochondrial dynamics is still not well understood. Here we aimed to investigate the effect of TGF-ß3 on mitochondrial dynamics of chondrocytes and reveal its underlying bio-mechanism. By using transmission electron microscopy (TEM) for the number and morphology of mitochondria, western blotting for the protein expressions, immunofluorescence for the cytoplasmic distributions of proteins, and RNA sequencing for the transcriptome changes related to mitochondrial dynamics. We found that TGF-ß3 could increase the number of mitochondria in chondrocytes. TGF-ß3-enhanced mitochondrial number was via promoting the mitochondrial fission. The mitochondrial fission induced by TGF-ß3 was mediated by AMPK signaling. TGF-ß3 activated canonical p-Smad3 signaling and resultantly mediated AMPK-induced mitochondrial fission. Taken together, these results elucidate an understanding of the role of TGF-ß3 on mitochondrial dynamics in chondrocytes and provide potential cues for therapeutic strategies in cartilage injury and OA disease in terms of energy metabolism.

Effects of ribonucleotide supplementation in modulating the growth of probiotic Bacillus subtilis and the synergistic benefits for improving the health performance of Asian seabass (Lates calcarifer).

In aquaculture, due to the requirements for high-density culture, the diseases caused by bacterial pathogens have become a serious issue. To solve this problem, we performed synbiotic application of RNA and Bacillus subtilis as a sustainable and eco-friendly approach to improve the health and immunity of Asian seabass (Lates calcarifer) during cultivation without using any harmful antibiotics or chemicals. Among various forms of nucleic acids, such as mononucleotides and DNA, RNA was found to be most effective in promoting the growth performance of probiotic B. subtilis in all the tested minimal medium conditions. Accordingly, we used the synbiotic combination of B. subtilis and RNA for Asian seabass cultivation. After feed supplementation for fourteen days, the fish that received the combination treatment exhibited a significant increase in innate cellular and humoral immune parameters, including phagocytic activity, phagocytic index, respiratory burst, serum lysozyme and bactericidal activities, as well as upregulated expression of immune-related genes, including HEPC1, A2M, C3, CC, CLEC, LYS, HSP70, and HSP90. Furthermore, significant increases were observed in the ileal villus height and goblet cell numbers in the intestinal villi in all fish treatment groups. The combination treatment did not cause histopathological abnormalities in the intestine and liver, suggesting that the synbiotic treatment is safe for use in fish. The treated Asian seabass also exhibited a significantly increased survival rate after Aeromonas hydrophila challenge. These results indicate that the synbiotic mixture of B. subtilis and RNA can be considered a beneficial feed additive and immunostimulant for Asian seabass cultivation.

[Developments in Research on Salivary Biomarkers in the Diagnosis of Systemic Diseases].

Saliva, an important biological fluid secreted by oral glands, serves multiple functions. It performs cleaning and protective functions for oral tissues, safeguarding against biological, mechanical and chemical stimuli, while allowing for the sensory perception of taste and temperature. It is also responsible for the preliminary digestion of food. These functions and properties of saliva are attributed to the presence of electrolytes, buffers, proteins, glycoproteins, and lipids in saliva. Recent studies have found that saliva contains biomarkers that are closely connected with the pathophysiological status of the human body, suggesting that saliva makes an ideal biological fluid for drug monitoring and biomarker screening. Therefore, salivary biomarkers can be used as an instrument for physical monitoring and localization of the occurrence of diseases, thereby accomplishing early diagnosis of diseases and assessment of the overall health status of patients. However, the actual application of salivary biomarkers in the diagnosis and treatment of systemic diseases is still not widely available, and the establishment of evaluation criteria and the exploration of its mechanism are not sufficiently investigated. Herein, we reviewed the latest research findings on applying the salivary biomarkers in the diagnosis of systemic diseases.

[New Developments in Research on the Relationship Between Osteoarthritis and Oral-Gut Microbes].

Osteoarthritis (OA) is the most common type of arthritis. The prevalence and the incidence of OA have been continuously growing along with increased life expectancy and the emerging problem of an aging population around the global. Reported findings have confirmed that osteoarthritis is a chronic inflammatory disease and its major risk factors included genetic susceptibility, aging, and environmental factors. However, the pathogenic mechanisms of osteoarthritis remain unclear. Recent studies have shown that oral-gut microbes are associated with the onset and development of osteoarthritis and may provide new targets for osteoarthritis treatment. Herein, we reviewed the latest developments in research on the relationship between oral-gut microbes and the onset and development of osteoarthritis, with a view to creating new perspectives for further elucidation of the pathogenesis of osteoarthritis and exploration of effective treatments in the future.

[Developments in Research on the Relationship Between Matrix Metalloproteinases and Osteoarthritis].

Matrix metalloproteinases (MMPs) acquired their names because they depend on metal ions such as Ca 2+ and Zn 2+ as their cofactors. Members of this family of proteins share a similar structure consisting of five functionally distinct structural domains. MMPs, including MMP-1, MMP-3, MMP-9, and MMP-13, are key substances that promote cartilage matrix degradation and play an important role in the occurrence and progression of osteoarthritis (OA). MMPs boost the development of OA through the degradation of extracellular matrix proteins of chondrocytes, the promotion of inflammation, and other mechanisms, and are hence attracting extensive and increasing attention from the medical community. OA is a common degenerative disease that occurs in the joints and is associated with aging, metabolism, infections, genetics, exercise, and other predisposing factors. The pathological changes it causes can lead to a series of clinical symptoms such as joint pain, morning stiffness, and restricted joint movement, severely affecting patients' quality of life. The pathogenic mechanism of this highly prevalent disease is still unclear. At present, there is no effective treatment available for disease improvement. In the future, selective inhibition of MMPs, the key enzymes, may become an effective therapeutic approach. Focusing on the pathogenic effects of MMPs in OA, we herein reviewed the latest findings on the role of MMPs in the occurrence and progression of OA.

The role of TGF-beta3 in cartilage development and osteoarthritis.

Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-ß3), a vital member of the highly conserved TGF-ß superfamily, plays a versatile role in cartilage physiology and pathology. TGF-ß3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-ß3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-ß3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-ß3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-ß3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-ß3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.

Rational Design of a Dual-Channel Fluorescent Probe for the Simultaneous Imaging of Hypochlorous Acid and Peroxynitrite in Living Organisms.

Hypochlorous acid (HOCl) and peroxynitrite (ONOO-) are two important highly reactive oxygen/nitrogen species, which commonly coexist in biosystems and play pivotal roles in many physiological and pathological processes. To investigate their function and correlations, it is urgently needed to construct chemical tools that can track the production of HOCl and ONOO- in biological systems with distinct fluorescence signals. Here, we found that the coumarin fluorescence of coumarin-benzopyrylium (CB) hydrazides (spirocyclic form) is dim, and their fluorescence properties are controlled by their benzopyran moiety via an intramolecular photo-induced electron transfer (PET) process. Based on this mechanism, we report the development of a fluorescent probe CB2-H for the simultaneous detection of HOCl and ONOO-. ONOO- can selectively oxidize the hydrazide group of CB2-H to afford the parent dye CB2 (Absmax/Emmax = 631/669 nm). In the case of HOCl, it undergoes an electrophilic attack on the benzopyran moiety of CB2-H to give a chlorinated product CB2-H-Cl, which inhibits the PET process within the probe and thus affords a turn-on fluorescence response at the coumarin channel (Absmax/Emmax = 407/468 nm). Due to the marked differences in absorption/emission wavelengths between the HOCl and ONOO- products, CB2-H enables the concurrent detection of HOCl and ONOO- at two independent channels without spectral cross-interference. CB2-H has been applied for dual-channel fluorescence imaging of endogenously produced HOCl and ONOO- in living cells and zebrafish under different stimulants. The present probe provides a useful tool for further exploring the distribution and correlation of HOCl and ONOO- in more biosystems.

[Latest Research Findings on Health Management Based on Saliva Testing].

Being one of the most important exocrine fluids of the human body, saliva can reflect the health status of the body. Soliva collection has various advantages--it is simple, painless, fast, and safe, and soliva can be collected multiple times a day. Therefore, it has been gradually applied in the exploration for biomarkers for disease detection, providing a basis for the monitoring of the course of diseases, medication monitoring, and efficacy evaluation. We should implement health management based on saliva testing, collect the medical data of the healthy and diseased individuals and monitor their whole life cycle health, perform clinical cohort study, aggregate the data on platforms for big data on health and medicine, manage and provide guidance for the health status of populations, pinpoint the high-risk factors for pathogenesis, and provide effective intervention, early warning, and assessment of the vital signs of individuals, thereby reinforcing health management of the whole life cycle and safeguarding people's health in an all-round way. In addition, it drives the development of the health industry and bears strategic significance for the promotion of national economic development. It is becoming a hot research topic promising great potential and impressive applicational prospects. Herein, we reviewed new techniques for clinical saliva testing and health management based on saliva testing.

Escherichia coli Can Eat DNA as an Excellent Nitrogen Source to Grow Quickly.

Is DNA or RNA a good nutrient? Although scientists have raised this question for dozens of years, few textbooks mention the nutritional role of nucleic acids. Paradoxically, mononucleotides are widely added to infant formula milk and animal feed. Interestingly, competent bacteria can bind and ingest extracellular DNA and even integrate it into their genome. These results prompt us to clarify whether bacteria can "eat" DNA as food. We found that Escherichia coli can grow well in the medium with DNA as carbon and nitrogen sources. More interestingly, in the presence of glucose and DNA, bacteria grew more rapidly, showing that bacteria can use DNA as an excellent nitrogen source. Surprisingly, the amount of DNA in the culture media decreased but its length remained unchanged, demonstrating that E. coli ingested long DNA directly. The gene expression study shows that E. coli mainly ingests DNA before digestion and digests it in the periplasm. Bifidobacterium bifidum can also use DNA as the nitrogen source for growth, but not efficiently as E. coli. This study is of great significance to study DNA metabolism and utilization in organisms. It also lays a foundation to understand the nutritional function of DNA in intestinal flora and human health.

Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction.

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology, proliferation, adhesion and differentiation, and even determining the cell fate. Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it. Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment, their regulatory network is not completely clear. In the current study, we generated silicon-based elastomer polydimethylsiloxane (PDMS) substrates with stiff (15:1, PDMS elastomer vs. curing agent) and soft (45:1) stiffnesses, which showed the Young's moduli of ~450 kPa and 46 kPa, respectively, and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein laminin ß1, focal adhesion complex protein FAK to microfilament bundling. We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses. We then found the changes of secreted extracellular linkage protein, laminin ß1, and focal adhesion complex protein, FAK, in chondrocytes in response to different substrate stiffnesses. These two proteins were shown to be directly interacted by Co-IP and colocalization. We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators. Taking together, this modulation axis of laminin ß1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing, mechanotransduction, and cytoskeleton re-organization.

Effect of D-cysteine on dual-species biofilms of Streptococcus mutans and Streptococcus sanguinis.

Dental caries is a highly prevalent disease worldwide. It is caused by the cariogenic biofilms composed of multiple dynamic bacteria on dental surface. Streptococcus mutans and Streptococcus sanguinis are resident members within the biofilms and an antagonistic relationship has been shown between these two species. S. mutans, as the major causative microorganism of dental caries, has been reported to be inhibited by free D-cysteine (D-Cys). However, whether D-Cys could affect S. sanguinis and the interspecies relationship between S. mutans and S. sanguinis remains unknown. The aim of the current study was to investigate the effect of D-Cys on the growth and cariogenicity of dual-species biofilms formed by S. mutans and S. sanguinis. We measured dual-species biofilms biomass, metabolic activity, lactate production. We also detected the biofilms structure, the ratio of live/dead bacteria, extracellular polysaccharide (EPS) synthesis and bacterial composition in the dual-species biofilms. We found that D-Cys could reduce the metabolic activity and lactic acid production of dual-species biofilms (p < 0.05). In addition, biofilms formation, the proportion of S. mutans in dual-species biofilms, and EPS synthesis were decreased with D-Cys treatment. The results suggested that D-Cys could inhibit the growth and cariogenic virulence of dual-species biofilms formed by S. mutans and S. sanguinis, indicating the potential of D-Cys in clinical application for caries prevention and treatment.