Cardiovascular disease represents a significant global cause of mortality, with its development and progression closely associated with pathological remodeling of cardiac tissue. Increasing attention has been directed towards environmental pollutants, particularly persistent organic pollutants (POPs), for their potential toxicity to the cardiovascular system. The effects of perfluorodecanoic acid (PFDA) on cardiac health remain inadequately understood. This study investigated the impact of PFDA exposure on cardiomyocyte aging and myocardial fibrosis, alongside the underlying mechanisms involved. Results indicated that PFDA treatment significantly induced cellular senescence and fibrosis-associated phenotypes in both rat H9c2 and mouse HL1 cardiomyocyte cell lines. CCK-8 assays demonstrated a reduction in cardiomyocyte viability following PFDA exposure. Western blot analyses revealed elevated senescence-associated markers, as well as a significant increase in the expression of key fibrotic markers. Additionally, PFDA exposure compromised mitochondrial function in cardiomyocytes, as evidenced by a decline in mitochondrial membrane potential and intracellular ATP levels. ELISA assays confirmed an increase in the secretion of inflammatory cytokines due to PFDA exposure. In vivo experiments utilizing C57BL/6 mice exposed to long-term low-dose PFDA displayed comparable pathological alterations in myocardial tissue. Immunohistochemical analysis revealed a significant increase in collagen fiber deposition within the myocardial interstitium of PFDA-exposed mice, alongside elevated expression levels of COLI and α-SMA compared to the control group. Mechanistically, PFDA exposure resulted in hyperactivation of the MTORC1 signaling axis, characterized by increased phosphorylation of its downstream substrates S6K1 and 4E-BP1 both in vitro and in vivo. Furthermore, activation of AKT was identified as an upstream event that contributes to MTORC1 hyperactivation. In summary, the environmental pollutant PFDA exacerbates cardiomyocyte senescence and activates cardiac fibroblasts through mechanisms that include mitochondrial dysfunction, inflammation promotion, and hyperactivation of the MTORC1 signaling cascade. This research provides novel experimental evidence supporting the role of PFDA pollutants in age-related cardiac diseases.

Recently, mesenchymal stem cells (MSCs) therapy has emerged as a revolutionary breakthrough in the treatment of T1DM. Nevertheless, its therapeutic efficacy is controversial due to the influence of diverse micro-environment including vitamin D (VD) deficiency. Moreover, it still remains unclear whether VD intervention could enhance the protective effects of MSCs via related pathways. Herein, the purpose of our study was to evaluate the roles of VD in augmenting the protective effects of MSCs on the pancreatic injury by affecting the inflammation, oxidative stress and mitophagy through both in vivo and in vitro experiments. Three-week-old male C57BL/6J mice were respectively fed with different VD diets for 3 weeks. Subsequently, a T1DM mouse model was established through intraperitoneal injection of streptozotocin (STZ) and then treated with MSCs via the tail vein. Then, their metabolic parameters, pancreatic histology, and indicators of oxidative stress and inflammation, as well as mRNA and protein expressions of related genes were analyzed in the serum, pancreatic and/or spleen tissues. Moreover, the roles of VD on the inflammation, oxidative stress, apoptosis, cellular and mitochondrial reactive oxygen species (ROS), and mitophagy were explored using the mouse islet β-cells (MIN-6) in vitro, which was then accurately verified by inhibiting the mitophagy as the Chloroquine (CQ). Herein, among the STZ-induced T1DM mice, VD interventions could effectively enhance the protective effects of MSCs on the insulin secretion and glucose metabolism in the VD+MSCs+T1DM group, as was evidenced by a significantly improved pancreatic β-cell structure, lower concentrations of serum glucose and higher glucose reserve capacity (P < 0.05). Simultaneously, it could alleviate the pancreatic injury, as manifested by higher expressions of Bcl-2/Bax and lower levels of Caspase 3 than those in the T1DM, VD+T1DM and/or MSCs+T1DM groups (P < 0.05). Moreover, comparing with the aforementioned three groups, VD+MSCs+T1DM group exhibited lower expressions of TNF-α, Foxp3, IL17A, cd68, Mcp1 and higher levels of Beclin-1, Pink1, Parkin in the pancreatic tissues, as well as higher contents of serum GSH, CAT, SOD and lower MDA (P < 0.05). Furthermore, comparing with the HG, VD + HG and/or MSCs + HG groups in vitro, VD + HG+MSCs interventions could ameliorate the percents of HG-induced cellular apoptosis, with lower expressions of Bax, Caspase 3 and TOMM20, and higher levels of genes related to VD metabolism such as CYP27A1, CYP24A1 and VDR (P < 0.05). Meanwhile, it could also reduce the contents of cellular and mitochondrial ROS with higher contents of SOD, CAT, GSH, GSH/GSSG and lower levels of MDA (P < 0.05). It was accompanied by the enhanced mitophagy, as indicated by higher expressions of Pink1 and Parkin, which could be partly diminished by inhibiting the mitophagy with CQ (P < 0.05). In sum, appropriate VD intervention both in vivo and vitro could ameliorate the inflammation, oxidative stress and mitophagy to enhance the protective effects of MSCs, suggesting that the clinicians ought to meticulously monitor the VD concentrations among the T1DM patients prior to contemplating the utilization of MSCs as a potential therapeutic approach in the future.

Intracranial germ cell tumors (iGCTs) are rare, histologically classified as extragonadal germ cell tumors, and predominantly affect children and adolescents. These tumors are commonly found in the midline of the brain, with a notable male predominance and varying geographic incidences. The origins of iGCTs have been debated, particularly whether they arise from abnormal migration of primordial germ cells (PGCs) or transformed embryonic stem cells (ESCs). In this study, we hypothesize the potential presence of PGC-like cells in the pituitary gland, and these cells may differentiate into iGCTs during the complex and frequent regulation of the hypothalamic-pituitary–gonadal axis (HPGA).We analyzed the expression of four germ cell markers—MVH, OCT4, C-kit, and PLZF—using immunohistochemistry, Western blotting, and real-time quantitative PCR in human pituitary tissues, pituitary tumors, and pituitary germ cell tumors. Our findings indicate significant expression of these markers in pituitary tissues, with the highest levels found in pituitary germ cell tumors. These results support the existence of PGC-like cells that within the normal pituitary gland. This study provides new insights into the cellular origins of iGCTs and suggests further investigation into the regulatory mechanisms that may lead to tumorigenesis.

[This retracts the article DOI: 10.1016/j.isci.2024.111262.].

Osteoradionecrosis of the jaw (ORNJ) is a severe complication of head and neck radiotherapy, characterized by a hostile tissue microenvironment that hinders healing. To address the limitations of mesenchymal stem cell (MSC) therapy, such as rapid dispersion and clearance, we developed an injectable, shear-thinning DNA supramolecular hydrogel (DNASH) as a 3D scaffold. The DNASH matrix significantly prolonged the local retention of MSCs and their exosomes for over 3 weeks. Crucially, the scaffold actively reprogrammed the MSC secretome by modulating the FAK‑Integrin and Hippo‑YAP mechanotransduction pathways. This directed a shift toward a pro-regenerative exosomal miRNA profile, notably enriching miR‑146a‑5p and reducing miR‑125b‑5p. In a murine ORNJ model, this MSC-laden hydrogel orchestrated a coupled bone-remodeling process, effectively clearing necrotic bone while stimulating robust osteogenesis. The treatment restored mandibular architecture, reduced systemic inflammation, and improved tissue homeostasis, presenting a clinically promising strategy for ORNJ repair.

MiRNA based nucleic acid therapeutics have been extensively investigated for the treatment of age-related diseases. However, efficient delivery of miRNA and effective therapy for age-related bone loss remain major challenges. In this study, we devised an engineered small extracellular vesicle (sEV) platform to address the dysregulation of bone homeostasis in the elderly. Initially, miR-126 was encapsulated into sEV to generate miR-126 loaded small extracellular vesicles (m-sEV), whose capacity to enhance vascularized bone regeneration was validatedin vitroand in a mandibular defect model of aged rats. To further optimize systemic therapeutic efficacy, we functionalized m-sEV with a bone-targeting peptide:(DSS)6, thereby constructing bone-targeting engineered vesicles (Bm-sEV). Systemic administration of Bm-sEV enabled precise miR-126 targeted delivery to bone tissue, resulting in increased abundance of type H vessels in the femur, improved bone microarchitecture, and attenuation of age-related bone loss. Mechanistic analyses demonstrated that the angiogenesis-osteogenesis coupling effect was mediated by upregulation of endothelial Integrinβ3 (ITGB3), which subsequently activated the ITGB3/ERK2 signaling cascade. Notably, Bm-sEV also restored the profoundly impaired osteoclastic activity in aged femurs, thereby re-establishing skeletal homeostasis. Collectively, Our study provides a promising approach for the treatment of age-related bone loss by combining biological macromolecules such as (DSS)6and miR-126 with sEV.

The poor viability and paracrine function of transplanted mesenchymal stem cells (MSCs) hamper their therapeutic efficacy in ischemic heart injury treatment. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have important functions in cellular responses. However, the role of PRMTs in MSC-based therapies for ischemic heart injury remains unclear. The aim of this study was to investigate the effect of PRMT1 on MSC function and therapeutic efficacy using a mouse myocardial infarction (MI) model. We isolated, cultured, and identified mouse adipose tissue-derived mesenchymal stromal cells (ADSCs). We used Furamidine, a PRMT1 inhibitor, and adenoviral shPRMT1 to study the effects of PRMT1 inhibition on ADSC proliferation, migration, and viability. We performed RNA sequencing and biochemical experiments to elucidate the molecular mechanisms of PRMT1 in ADSCs. Finally, we infected ADSCs with adenoviral shPRMT1 and administered an intramyocardial injection after MI. Cardiac function was evaluated using echocardiography and pathological staining, and ADSCs survival rates, cardiomyocyte apoptosis, and capillary density were evaluated using immunofluorescence staining. We found that PRMT1 was highly expressed in ADSCs and markedly upregulated in response to H2O2 challenge. Inhibition of PRMT1 by Furamidine or adenoviral shPRMT1 promoted ADSC proliferation and migration and reduced H2O2-induced ADSCs apoptosis. Mechanistically, PRMT1 inhibition significantly increased the expression of matrix metallopeptidase (MMP)-10, placenta growth factor (PlGF) and transforming growth factor (TGF)-β2 in ADSCs through transcription factor RUNX1. Blockage of RUNX1 abolished the proliferative and migratory effects of PRMT1 inhibition in ADSCs. Compared to ADSCs infected with the adenovirus-control, PRMT1 knockdown adenovirus markedly increased the survival and retention of transplanted ADSCs in injured hearts after MI. ADSCs with PRMT1 knockdown markedly improved cardiac function and alleviated cardiac fibrosis in mice after MI by reducing cardiomyocyte apoptosis and increasing capillary density. PRMT1 inhibition enhances the cardioprotective effect of ADSCs against MI through RUNX1-mediated production of MMP-10/PlGF/TGF-β2. Overall, PRMT1 inhibition is a promising strategy for augmenting MSCs therapeutic efficacy in ischemic cardiomyopathy.

Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential in the treatment of type 1 diabetes mellitus (T1DM); however, the underlying mechanism remains unclear. The primary pathological mechanism of T1DM involves activated T cells infiltrating the pancreas, leading to islet inflammation and the destruction of β-cells. However, the question of whether exosomes derived from MSCs can suppress the migration of T cells to the pancreas in the context of T1DM remains unresolved. In this study, we observed that miR-25 was highly expressed in MSCs exosomes and associated with signaling pathways related to cell migration. In vitro assay, we synthesized a miR-25 mimic and transiently transfected it into activated T cells, which revealed that miR-25 can effectively reduce the expression of CXCR3. Additionally, according to the in vivo T1DM mouse model, we found that there was a significant increase in miR-25 levels in T1DM mice treated with MSCs and the number of T cells decreased. Overall, our findings suggest that MSCs exosomes containing miR-25 can impede the infiltration of activated T cells into the pancreas in T1DM by repressing CXCR3 expression in these cells.

Diabetic kidney disease (DKD) is still as a common chronic micro-vascular complication of type 1 diabetic (T1DM). Although many studies had verified the therapeutic potential of mesenchymal stem cells (MSCs) on the clinical treatment of the related complications associated with T1DM, especially the DKD, by preserving the balances of immune micro-environment and so on. However, the immunomodulatory capabilities of MSCs are still controversial on the the efficacy of DKD treatment primarily due to the variations on the immune micro-environment, which could be modulated by a variety of elements, such as the vitamin D (VD). Otherwise, its underlying molecular mechanisms have not yet been elucidated. Herein, the purpose of our study was to explore the synergistic effects of co-treatments with VD and MSCs in vivo and in vitro on the progression of DKD by attenuating the SIRT1-mediated pathways. Four-week-old male mice were fed with different VD diets for four weeks and established the T1DM models by administering the STZ (40 mg/kg) via intraperitoneal injection, which were then treated with BMSCs (bone MSCs) injection through the tail vein. After the euthanasia, the renal functions, pathological productors and VD metabolites were evaluated by the related biochemical indicators, flow cytometry analysis, staining techniques and immunofluorescence in the serum and/or renal tissues. Meanwhile, the mechanisms of SIRT1-mediated pathways underlying the amelioration of co-treatment with VD and MSCs on the renal injuries were examined by qRT-PCR, Western blotting and immunohistochemistry assays, which were then verified by the MPC5 cells in vitro with SIRT1-specific knockdown and over-expression under the treatment of high glucose (HG). Totally, co-treatments of VD and MSCs could more effectively ameliorate the disorders of glucose metabolism and renal injuries (KIM1, Podocin, ZEB1 and/or ZEB2) by boosting the concentrations of VD metabolites both in the STZ-induced T1DM mice models and MPC5 cells with HG treatment in vitro (P < 0.05). Moreover, the mechanism results indicated that co-treatments of VD and MSCs could improve the DKD such as the renal inflammation and fibrosis by attenuating the SIRT1 to inhibit the activation of TGFβ1/Smad pathways both in vivo and in vitro (P < 0.05). Furthermore, over-expression of SIRT1 could partly abolish the inflammation and fibrosis in vitro by attenuating the SIRT1-mediated TGFβ1/Smad3 pathways, which might be aggravated under the down-regulated expressions of SIRT1 in vitro (P < 0.05). Our findings had detailed the mechanisms underlying the amelioration of VD and MSCs related SIRT1-mediated pathways agonist on the DKD-like pathology both in vivo and in vitro, which could highlight the important potential of SIRT1 as a promising therapeutic target for the progression of DKD.

Nowadays mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising cell-free therapeutic alternative to MSC-based therapies, demonstrating efficacy in treating degenerative diseases, inflammatory disorders, and autoimmune diseases. MSC-Exos transport bioactive cargoes such as proteins, lipids, mRNAs, and microRNAs (miRNAs) to the recipient cells, mediating intercellular communication to regulate immunomodulation and tissue repair. However, the exosomal miRNA profile varies dynamically based on the culture conditions and tissue sources. Thus, elucidating the specific exosomal miRNA profile and regulatory targets is critical for the precise clinical applications and development of MSC-Exos-based cell-free therapies.Here we established an optimized serum-free culture system for human umbilical cord-derived MSCs (hUC-MSCs) and determined the critical 48–72-h harvest window for exosome secretion. High-throughput sequencing identified miR-16-5p as the predominant exosomal miRNA, functioning as a core immunosuppressive effector by suppressing LPS/IFN-γ-induced M1 macrophage polarization and Th1 cell differentiation. Mechanistically, miR-16-5p was found to target key nodes in NF-κB and JAK-STAT pathways, validated via dual-luciferase assays. Additionally, miR-125b-5p and miR-34a-5p enhanced this immunosuppressive effect by co-targeting overlapping pathway components in NF-κB and JAK-STAT pathways, suggesting a multilayered regulatory network. Taken together, our findings highlight the potential of miRNA-engineered exosomes as standardized therapies for inflammatory disorders, emphasizing the importance of optimizing culture conditions and profiling miRNA expression over time in advancing clinical translation.

The emergence of extracellular vesicles (EVs), which are natural lipid bilayer membrane structures facilitating intercellular substance and information exchange, has sparked innovative approaches in drug development and carrier enhancement. Plant-derived EVs notably offer advantages including low preparation cost, low immunogenicity, flexible drug delivery, high stability, good tissue permeability, and high inherent medicinal value compared to their animal-derived counterparts. Despite these promising attributes, the research on plant-derived EVs remains fragmented and lacks comprehensive synthesis. This review aims to address this gap by summarizing the isolation methods, biological characteristics, and storage techniques of plant-derived EVs. Additionally, we explore the potential of plant-derived EVs as therapeutic agents and drug carriers for treating various diseases. Finally, we delineate the current impediments to plant-derived EV development and highlight future research directions. By providing a detailed overview, we hope to facilitate further research and application in this emerging field.

The character "(sic) (j & iacute;)" in Chinese shares the meaning of "is", indicating an identity or equivalence between two concepts. In this framework, one might expect the antecedent and the consequent of "(sic)" to be identical in meaning, or at least for a term with a positive connotation not to be paired with one of negative connotation. However, in Tiantai Buddhism, many core propositions follow the structure "x (sic) y", where x is negative and y is positive, or vice versa. This suggests an identity between opposites, creating a paradoxical feature in the system. This essay argues that the paradox within Tiantai Buddhism is a veridical paradox, as defined by Quine, meaning it can be resolved in various ways and does not reflect a genuine contradiction in reality. While Western Buddhist philosophers and logicians have focused primarily on the paradoxes in N & amacr;g & amacr;rjuna's thought, this essay demonstrates that Chinese Tiantai Buddhism offers practical resolutions to these paradoxes. The paper first explicates the paradox by examining its roots in Buddhist history, then explores responses to it. Finally, different methods for resolving the paradox are compared and evaluated.

Background: The predictive value of growth differentiation factor-15 (GDF-15) in coronary microvascular dysfunction (CMD) following primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) patients is unclear. Methods: This study continuously recruited STEMI patients treated with PPCI at the Chest Pain Center of Qilu Hospital of Shandong University from April 2023 to December 2023. Blood samples were taken before PPCI and the level of circulating GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the patients were divided into CMD and Control group according to angiographic microvascular resistance (AMR) (cut-off value 2.50 mmHg*s/cm). The differences in GDF-15 expression levels between the two groups were compared, and the predictive value of GDF-15 for CMD was systematically evaluated. Results: A total of 134 patients, with an average age of 59.78 +/- 12.69 years and 75.37 % being male, were included in this study. Multivariable logistic regression revealed a significant association between GDF-15 and CMD (adjusted OR = 2.505, 95 % CI: 1.661-3.779, P < 0.001). The area under the curve (AUC) of GDF-15 for CMD was 0.782 (95 % CI: 0.704-0.861), with a sensitivity of 0.795 and specificity of 0.643 in predicting CMD in PPCI. The AUC of the GDF-15 model (Model With GDF-15) was 0.867 (95 % CI: 0.806-0.928), significantly outperforming the clinical baseline model (Model Without GDF-15) (Delta AUC = 0.079, 95 % CI: 0.020-0.138, P = 0.009). Furthermore, the net reclassification improvement (NRI) was 0.854 (95 % CI: 0.543-1.166, P < 0.001), and the integrated discrimination improvement (IDI) was 0.151 (95 % CI: 0.089-0.213, P < 0.001). Conclusions: GDF-15 can serve as a biomarker for predicting the development of CMD in STEMI patients undergoing PPCI.

Acute lung injury (ALI) has been a hot topic in the field of critical care research in recent years. Mitochondrial dynamics consists of mitochondrial fusion and mitochondrial fission. Dynamin-related protein 1 (Drp1), a key molecule that regulates mitochondrial fission, is important in the oxidative stress and inflammatory response to ALI. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a core protein that mediates mitochondrial biogenesis. G-protein pathway suppressor 2 (GPS2) acts as a transcriptional cofactor with regulatory effects on nuclear-encoded mitochondrial genes. This study aimed to investigate the mechanism of PGC-1α/Drp1-mediated mitochondrial dynamics involved in ALI and to demonstrate the protective mechanism of GPS2 in regulating mitochondrial structure and function and inflammation in ALI. The ALI model was constructed using LPS-induced wild-type mice and human pulmonary microvascular endothelial cells (HPMVECs). It was found that lung injury, oxidative stress and inflammation were exacerbated in the mice ALI model and that mitochondrial structure and function were disrupted in HPMVECs. In vitro studies revealed that LPS led to the upregulated expression of Drp1 and the downregulated expression of PGC-1α and GPS2. Mitochondrial division was reduced and respiratory function was restored in Drp1 knockdown cells, which inhibited oxidative stress and inflammatory response. In addition, the overexpression of PGC-1α and GPS2 significantly inhibited the expression of Drp1, mitochondrial function was restored, and inhibited reactive oxygen species (ROS) production and inflammatory factor release. Moreover, the overexpression of GPS2 promoted the upregulated expression of PGC-1α. This mechanism was also validated in vivo, in which the low expression of GPS2 in mice resulted in the upregulated expression of Drp1 and the downregulated expression of PGC-1α, and further exacerbated LPS-induced ALI. In the present study, we also found that LPS-induced the downregulated expression of GPS2 may be associated with its increased degradation by the proteasome. Therefore, these findings revealed that GPS2 inhibited oxidative stress and inflammation by modulating PGC-1α/Drp1-mediated mitochondrial dynamics to alleviate LPS-induced ALI, which may provide a new approach to the therapeutic orientation for LPS-induced ALI.

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1β secretion.

Obesity is characterized by excessive fat accumulation, which is related with abnormal pluripotency of mesenchymal stem cells (MSCs). Recently, there is growing evidence that the disorder of maternal vitamin D (VD) intake is a well-known risk factor for long-term adverse health outcomes to their offspring. Otherwise, less is known of its repercussion and underlying mechanisms on the different differentiation potential of MSCs. Four-week-old female C57BL/6J mice were fed with different VD reproductive diets throughout the whole pregnancy and lactation. The characteristics of BMSCs from their seven-day male offspring, VDR knockdown establishment of HuMSCs and HuMSCs under the different VD interventions in vitro were confirmed by flow cytometry, RT-PCR, and immunofluorescence. The roles of VD on their mitochondrial dysfunction and differentiation potential were also investigated. Then their remaining weaned male pups were induced by administrating high-fat-diet (HFD) for 16 weeks and normal fat diet was simultaneously as controls. Their lipid accumulation and adipocytes hypertrophy were determined by histological staining and related gene expressions. Herein, it was proved that imbalance of early-life VD intake could significantly aggravate the occurrence of obesity by inducing the adipogenesis through affecting the VD metabolism and related metabolites (P < 0.05). Moreover, abnormally maternal VD intake might be involved on the disorders of differentiation potential to inhibit the maintenance of MSCs stemness through increasing the productions of ROS, which was accompanied by impairing the expression of related genes on the adipo-osteogenic differentiation (P < 0.05). Moreover, it was along with increasing potential of adipogenic differentiation of MSCs as higher ROS in the state of VD deficiency, while excessive maternal VD status could conversely enhance the osteogenic differentiation with slightly lower ROS (P < 0.05). Furthermore, the underlying mechanisms might be involved on the mitochondria dysfunctional, especially the mitophagy, by activating the LC3b, P62 and etc. using in vivo and in vitro studies (P < 0.05). These findings demonstrated that imbalance of early-life VD intake could target ROS-mediated crosstalk between mitochondrial dysfunction and differentiation potential of MSCs, which was significantly associated with the later obesity. Obviously, our results could open up an attractive modality for the benefits of suitable VD intake during the pregnancy and lactation.

In the study, lycopene and resveratrol nanoemulsion hydrogel beads were prepared by using agarose‑sodium alginate as a carrier and the semi-interpenetrating polymer network technique, characteristics and morphologies were evaluated by scanning electron microscopy, fluorescence microscopy, rheological measurement. The synergistic antioxidant effect of lycopene and resveratrol was confirmed, the best synergistic antioxidant performance is achieved when the ratio of 1:1. To increase the solubility and improve the stability, the lycopene was prepared as solid dispersion added to the nanoemulsion. The encapsulation rate of lycopene and resveratrol reached 93.60 ± 2.94 % and 89.30 ± 1.75 %, respectively, and the cumulative release showed that the addition of agarose slowed down the release rate of the compound, which improves the applicability of lycopene and resveratrol and development of carriers for the delivery of different bioactive ingredients.

The term “peri-implantitis” (peri-implantitis) refers to an inflammatory lesion of the mucosa surrounding an endosseous implant and a progressive loss of the peri-implant bone that supports the implant. Recently, it has been suggested that the increased sensitivity of implants to infection and the quick elimination of supporting tissue after infection may be caused by a dysregulated peri-implant mucosal immune response. Macrophages are polarized in response to environmental signals and play multiple roles in peri-implantitis. In peri-implantitis lesion samples, recent investigations have discovered a considerable increase in M1 type macrophages, with M1 type macrophages contributing to the pro-inflammatory response brought on by bacteria, whereas M2 type macrophages contribute to inflammation remission and tissue repair. In an effort to better understand the pathogenesis of peri-implantitis and suggest potential immunomodulatory treatments for peri-implantitis in the direction of macrophage polarization patterns, this review summarizes the research findings related to macrophage polarization in peri-implantitis and compares them with periodontitis.

BACKGROUND:Cardiovascular consequences of phthalates exposure have been given increasing attention, but the association of phthalates with subclinical cardiovascular disease (CVD) was unknown. Accordingly, this study aimed to investigate the association between phthalates exposure and high-sensitivity cardiac troponin I (hs-cTnI), a marker of myocardial injury, which was detectable in the subclinical stage of CVD. METHODS:Participants aged 6 years or older with available urinary phthalates metabolites and serum hs-cTnI concentrations were included in the National Health and Nutrition Examination Survey 2003-2004 cycle. Multivariable linear regression and weighted quantiles sum (WQS) regression were used to assess the association of hs-cTnI with individual phthalates and their co-exposure. Di-2-ethylhexylphthalate (ΣDEHP), high-molecular-weight phthalate (ΣHMWP), and low-molecular-weight phthalate (ΣLMWP) were defined as the molecular sum of phthalates metabolites in urine. RESULTS:2241 participants were finally included. The percent change of serum hs-cTnI concentrations related to per 1-standard deviation increase of logarithmic urinary phthalates concentrations was 3.4% (0.1-6.7, P = 0.04) for ΣDEHP, 3.6% (0.3-6.9, P = 0.03) for ΣHMWP, and 3.5% (0.2-6.8, P = 0.04) for ΣLMWP. Co-exposure to phthalates metabolites expressed as the WQS index also demonstrated a positive association with hs-cTnI. A similar association pattern was found in the population with no prior CVD. CONCLUSIONS:This study indicated the potential of phthalates to myocardial injury which may occur even before clinically apparent CVD was identified, emphasizing the significance of reducing phthalates in the prevention of CVD.