Production Of Metalloproteinases Research Articles

Inhibition of nitric oxide production in RAW 264.7 cells and cytokines IL-1β in osteoarthritis rat models of 70 % ethanol extract of Arcangelisia flava (L.) merr stems

IntroductionOne of the most frequent types of arthritis is osteoarthritis, also referred to as a degenerative joint disease. Interleukin-1β (IL-1β) and nitric oxide (NO) are essential factors in the pain response; IL-1β and NO are responsible for increasing the production of matrix metalloproteinases (MMP) and a disintegrin-like and metalloproteinases with thrombospondin motifs (ADAMS) in chondrocytes. Arcangelisia flava (L.) Merr. Has been traditionally used to treat jaundice, liver disease, diarrhea, fever, and inflammation. MethodsThis study used in vitro and in vivo models to determine the effect of a 70 % ethanol extract of Arcangelisia flava (L.) Merr. stems on the inhibition of NO production in RAW 264.7 cells induced with lipopolysaccharide (LPS) and IL-1β in osteoarthritis rats induced with monosodium iodoacetate (MIA). The NO inhibition test was determined by the NO colorimetric assay using Griess reagent and measured by the ELISA plate reader. The measurement of joint diameter and hyperalgesia in osteoarthritis rats was carried out once a week for 7 weeks, and then the IL-1β levels were measured at weeks 3 and 7. ResultThe viability of cell line this extract was greater than 80 %, and the extract at 25, 50, and 100 μg/mL significantly inhibited NO production (p < 0.0001) in RAW 264.7 cells induced with LPS. Meanwhile, this extract at 10, 30, and 90 mg/200g BW increased latency time, reduced joint swelling, and reduced IL-1β levels in the serum in the osteoarthritis rat model. Conclusion70 % ethanol extract of Arcangelisia flava (L.) Merr. Has the potential to be an anti-osteoarthritis drug.

A novel chitosan-PEG hydrogel embedded with in situ silver nanoparticles of Clerodendrum glandulosum Lindl. extract: evaluation of its in vivo diabetic wound healing properties using an image-guided machine learning model.

The pathophysiology of chronic wounds related to diabetes mellitus is a result of a series of complications induced by hyperglycemia. The symptoms include impaired growth factor production, decreased keratinocyte proliferation and migration, reduced angiogenesis and cytokine synthesis, lowered matrix metalloproteinase (MMP) production, neuropathy, reduced nitric oxide synthase production, decreased fibroblast synthesis and migration, and impaired inflammatory cell functions. This multifaceted mechanism of diabetic wounds needs a suitable novel topical formulation that can deliver the active constituent by a controlled means, target the various stages of wound healing, absorb the wound exudates, and prevent secondary infections. To meet the above requirements, the Clerodendrum glandulosum (CG) extract reduced silver nanoparticle (AgNP) impregnated chitosan-polyethylene glycol (PEG) hydrogel was synthesized. The findings of the physicochemical characterization studies suggested that the hydrogel exhibited excellent formulation characteristics and showed controlled release for seven days, making it suitable for chronic wound healing studies. In subsequent studies, these formulations showed good antioxidant and antimicrobial properties, and hemocompatibility, with the least cytotoxic properties. The results of the diabetic wound healing studies showed a faster wound closure rate and improved extracellular matrix formation. These antioxidant, antimicrobial, anti-inflammatory and wound-healing properties suggest that the CG-AgNP loaded chitosan-PEG hydrogel is a promising material for novel topical formulation of diabetic wounds.

Acetyl-11-keto-β-boswellic acid restrains the progression of synovitis in osteoarthritis via the Nrf2/HO-1 pathway.

Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-β-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

Combination of Nicotinamide and Agastache rugosa Extract: A Potent Strategy for Protecting Hs68 Cells from UVB-Induced Photoaging.

This study investigated the protective effects of nicotinamide (NAM) and Agastache rugosa extract (AR) against ultraviolet B (UVB)-induced photoaging in Hs68 cells. The results demonstrated that NAM and AR, alone or in combination, exhibited concentration-dependent protective effects against UVB radiation. The highest synergistic effect was observed at a NAM:AR ratio of 6:4. This combination exhibited a synergistic protective effect against UVB-induced photoaging. The sample concentration required for 80% cell survival was 9.70 μM and 131.16 ppm for NAM and AR, respectively. However, when combined, they exhibited strong synergistic effects with concentrations as low as 0.11 μM and 17.50 ppm. Moreover, 5.26 μM of NAM and 1,082.13 ppm of AR were required to inhibit 30% of reactive oxygen species, but the combination treatment required 0.62 μM and 95.49 ppm, respectively. This combination significantly reduced the production of matrix metalloproteinase and increased collagen production. These findings highlight the potential of combining NAM and AR as functional cosmetic materials to protect against UVB-induced photoaging. The synergistic effects observed in this study provide valuable information for developing novel strategies for cosmetic combinations that target UVB-mediated skin damage.

NF-κB/RelA signaling in secretoglobin progenitors mediates plasticity and MMP-induced barrier disruption in house dust mite-induced allergic asthma.

The mechanisms how aeroallergens induce sensitization are incompletely understood. The house dust mite (HDM) Dermatophagoides pteronyssius (Der p) is a ubiquitous aeroallergen that represents a major cause of allergic rhinitis and asthma. Herein, we tested whether HDM-induced aeroallergen exposure sensitivity is caused by the innate-immune response in small airway epithelial cells. HDM exposure is a rapid activator of NF-κB/RelA in the Secretoglobin (Scgb1a1+) lineage associated with upregulation of NF-κB/RelA-dependent markers of epithelial plasticity. To determine the effect of epithelial NF-κB signaling, NF-κB was depleted in a tamoxifen (TMX)-inducible Scgb1a1-CreERTM mouse within a CL57B/L6 background. Corn oil or TMX-treated/RelA-depleted [RelA knockdown (KD)] mice were repetitively exposed to airway HDM challenges to induce airway hyperresponsiveness (AHR). Strikingly, we observed that HDM induces hallmarks of epithelial plasticity through upregulation of the mesenchymal core factors SNAI1 and ZEB1 and production of metalloproteinase (MMP)9 that are RelA-dependent. Downstream, HDM-induced mucous metaplasia, Th2 polarization, allergen sensitivity, and airway hyperreactivity were all reduced in the RelA-depleted mice. Mechanistically, HDM-induced functional and structural barrier disruption was dependent on RelA signaling and associated with active MMP secretion into the bronchoalveolar lavage fluid. To establish the role of MMP2/9 in barrier disruption, we observe that a small-molecule MMP inhibitor (SB-3CT) blocked HDM-induced barrier disruption and activation of plasticity in naïve wild-type (WT) mice. Loss of functional barrier was associated with MMP disruption of zona occludens (ZO)-1 containing adherens junctions. Overall, this data indicates that host innate signaling in the Scgb1a1+ progenitors is directly linked to epithelial plasticity, MMP9 secretion, and enhanced barrier permeability that allows allergen penetration, sensitization producing allergic asthma (AA) in vivo. We propose that maintenance of epithelial integrity may reduce allergic sensitization and AA.NEW & NOTEWORTHY Allergic asthma from house dust mite (HDM) allergy causes substantial morbidity. This study examines the dynamic changes in small airway epithelial cells in a mouse model of HDM exposure. Our findings indicate that NF-κB/RelA signaling mediates matrix metalloproteinase production, disrupting the epithelial barrier resulting in allergic sensitization. Our findings bring new insight into mechanisms for epithelial cell-state change in the allergen response, creating a potential therapeutic pathway for maintaining barrier function in asthma.

Investigation of multinucleation and apoptosis of macrophages of BCG-infected mice and their production of cathepsins and matrix metalloproteinases

The relevance of the study of the role of macrophages and their multinucleated forms in the pathogenesis of tuberculous granulomatosis is determined by its wide prevalence, the presence of severe socio-economic consequences of its morbidity and necrotic complications, which are based on the high destructive potential of macrophages associated with the role of hydrolases in the degradation of extracellular matrix components. Aim of the study was to investigate the features of the multinucleation, apoptosis and expression of a number of hydrolases in macrophages of BCG-infected mice. Material and methods. The intensity of macrophage multinucleation and apoptosis, the peculiarities of their expression of matrix metalloproteinases (MMP-1, MMP-9), catepsins (CatB, CatD), caspase-3, and p53 protein were studied in peritoneal cells cultures of intact and BCG-infected BALB/c mice. Results. The number of multinucleated macrophages increased according to the terms of the experiment, having a maximum value for 3 months of observation, but after 2 months almost reaching this level. The realization of apoptosis, multinucleation of macrophages had a complex character, determining the composition of their subpopulations. The dynamics of the expression of the studied hydrolases by macrophages indicated their unequal role in tissue necrosis at various stages of granulomogenesis. The high functional ability of multinucleated macrophages to produce hydrolases of certain types is shown. Intense expression of MMP-1 in the early stages of granulomogenesis and its maximum value, as well as CatD expression for 3 months, and strong expression of MMP-9 for 6 months were noted. Conclusions. Stimulation of plastic processes in macrophages under conditions of BCG-granulomatosis determines the formation of multinucleated macrophages with high functional potential and intensive expression of hydrolases by macrophages for 2 and 3 months of granulomogenesis. These are periods of high risk of necrotic complications of tuberculous granulomatosis, which should be taken into account when developing methods for their prevention and therapeutic correction.

Effects of a low, medium, and high-intensity aquatic physiotherapy protocol on functional and biochemical parameters in individuals with knee osteoarthritis: protocol for a crossover randomized controlled trial

Background Knee osteoarthritis affects the performance of daily activities, independence, and quality of life. The etiopathogenesis of this condition considers the mechanisms of activation of metalloproteinase and reactive oxygen species production pathways. Metalloproteinases-3 (MMP-3) and Glutathione Peroxidase (GPx) may be responsible for cartilage destruction. Aquatic physiotherapy promotes a positive impact on the clinical picture of osteoarthritis, and this study presents an intervention protocol that aims to evaluate the effects of a single session of different aquatic physiotherapy modalities on the biochemical and functional behavior of patients with knee osteoarthritis. Methods This will be a crossover randomized controlled trial in which 15 individuals will be submitted to three aquatic physiotherapy modalities with a minimum 15-day wash-out period in patients over 50 years old and diagnosed with OA in at least one knee, presence of pain and at least one functional dysfunction for at least 6 months, absence of physical limitation that prevents the exercise protocol from being performed, Kellgren and Lawrence ranking between I and IV, walk independently and without auxiliary device. Variations in the concentrations of MMP-3 and GPx in peripheral blood, pain, edema, and flexibility resulting from the three aquatic physiotherapeutic interventions will be evaluated both pre- and immediate post-intervention. The reference group will be submitted to the same aquatic physiotherapy protocols, however, only the biochemical parameters and the self-perception questionnaires will be evaluated. Registration ClinicalTrials.gov (NCT05610696, 18/01/2023).

Generation of 3D melanoma models using an assembloid-based approach

While 3D tumor models have greatly evolved over the past years, there is still a strong requirement for more biosimilar models which are capable of recapitulating cellular crosstalk within the tumor microenvironment while equally displaying representative levels of tumor aggressiveness and invasion. Herein, we disclose an assembloid melanoma model based on the fusion of individual stromal multicellular spheroids (MCSs). In contrast to more traditional tumor models, we show that it is possible to develop self-organizing, heterotypic melanoma models where tumor cells present stem-cell like features like up-regulated pluripotency master regulators SOX2, POU5F1 and NANOG. Additionally, these assembloids display high levels of invasiveness while embedded in 3D matrices as evidenced by stromal cell promotion of melanoma cell invasion via metalloproteinase production. Furthermore, sensitivity to anticancer drug doxorubicin was demonstrated for the melanoma assembloid model. These findings suggest that melanoma assembloids may play a significant role in the field of 3D cancer models as they more closely mimic the tumor microenvironment when compared to more traditional MCSs, opening the doors to a better understanding of the role of tumor microenvironment in supporting tumor progression. Statement of significanceThe development of complex 3D tumor models that better recapitulate the tumor microenvironment is crucial for both an improved comprehension of intercellular crosstalk and for more efficient drug screening. We have herein developed a self-organizing heterotypic assembloid-based melanoma model capable of closely mimicking the tumor microenvironment. Key features recapitulated were the preservation of cancer cell stemness, sensitivity to anti-cancer agents and tumor cell invasion promoted by stromal cells. The approach of pre-establishing distinct stromal domains for subsequent combination into more complex tumor constructs provides a route for developing superior tumor models with a higher degree of similarity to native cancer tissues.

A Model for Membrane Degradation Using a Gelatin Invadopodia Assay.

One of the most crucial and lethal characteristics of solid tumors is represented by the increased ability of cancer cells to migrate and invade other organs during the so-called metastatic spread. This is allowed thanks to the production of matrix metalloproteinases (MMPs), enzymes capable of degrading a type of collagen abundant in the basal membrane separating the epithelial tissue from the connective one. In this work, we employ a synergistic experimental and mathematical modelling approach to explore the invasion process of tumor cells. A mathematical model composed of reaction-diffusion equations describing the evolution of the tumor cells density on a gelatin substrate, MMPs enzymes concentration and the degradation of the gelatin is proposed. This is completed with a calibration strategy. We perform a sensitivity analysis and explore a parameter estimation technique both on synthetic and experimental data in order to find the optimal parameters that describe the in vitro experiments. A comparison between numerical and experimental solutions ends the work.

Osmolarity-Induced Altered Intracellular Molecular Crowding Drives Osteoarthritis Pathology.

Osteoarthritis (OA) is a multifactorial degenerative joint disease of which the underlying mechanisms are yet to be fully understood. At the molecular level, multiple factors including altered signaling pathways, epigenetics, metabolic imbalance, extracellular matrix degradation, production of matrix metalloproteinases, and inflammatory cytokines, are known to play a detrimental role in OA. However, these factors do not initiate OA, but are mediators or consequences of the disease, while many other factors causing the etiology of OA are still unknown. Here, it is revealed that microenvironmental osmolarity can induce and reverse osteoarthritis-related behavior of chondrocytes via altered intracellular molecular crowding, which represents a previously unknown mechanism underlying OA pathophysiology. Decreased intracellular crowding is associated with increased sensitivity to proinflammatory triggers and decreased responsiveness to anabolic stimuli. OA-induced lowered intracellular molecular crowding could be renormalized via exposure to higher extracellular osmolarity such as those found in healthy joints, which reverse OA chondrocyte's sensitivity to catabolic stimuli as well as its glycolytic metabolism.

Clinical studies and meta-analysis on the effects of collagen, vitamin, and nutrient supplementation for the rejuvenation of collagenic fibers: a systematic review

Introduction: Collagen prevails in connective tissues, constituting 80% of the dry weight of human skin. Aging induces a decline in enzymes involved in the post-translational processing of collagen, reducing the number of fibroblasts that synthesize collagen and the vessels that irrigate the skin. Oral ingestion of hydrolyzed collagen together with vitamins and nutrients (especially apple exosomes) increases the levels of collagenderived peptides in the bloodstream and improves skin properties. Objective: It was to carry out a systematic review to elucidate the main results of clinical studies and meta-analyses of clinical studies on the effects of supplementation of types of collagen, vitamins, and nutrients for the rejuvenation of collagen fibers. Methods: The search was carried out from October to December 2023 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 122 articles were found, and 12 articles were evaluated in full, and 07 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 20 studies with a high risk of bias and 26 studies that did not meet GRADE and AMSTAR-2. Most studies showed homogeneity in their results, with X2=62.4%&gt;50%. Oral nutritional supplements containing collagen peptides can reduce skin vulnerability in the elderly and thus prevent conditions such as skin lesions. The direct effects of collagen peptides on fibroblasts, M2-like macrophages, and mechanisms related to oral tolerance are the possible mechanisms for the beneficial effects of collagen supplementation. Special collagen peptides together with acerola extract, vitamin C, vitamin E, biotin, and zinc showed a significant improvement in the skin's collagen structure. The proven positive nutritional effect on collagen structure was fully consistent with the quality of healthy skin. Finally, apple-derived nanovesicles (exosomes) also reduce the degradation of the extracellular matrix, increasing collagen synthesis (COL3A1, COL1A2, COL8A1, and COL6A1) and negatively regulating the production of metalloproteinases.

Urolithin B reduces cartilage degeneration and alleviates osteoarthritis by inhibiting inflammation.

Osteoarthritis is the most prevalent degenerative joint disease reported worldwide. Conventional treatment strategies mainly focus on medication and involve surgical joint replacement. The use of these therapies is limited by gastrointestinal complications and the lifespan of joint prostheses. Hence, safe and efficacious drugs are urgently needed to impede the osteoarthritis progression. Urolithin B, a metabolite of ellagic acid in the gut, exhibits anti-inflammatory and antioxidant properties; however, its role in osteoarthritis remains unclear. In this study, we demonstrated that urolithin B efficiently inhibits the inflammatory factor-induced production of matrix metalloproteinases (MMP3 and MMP13) in vitro and upregulates the expression of type II collagen and aggrecan. Urolithin B alleviates cartilage erosion and osteophyte formation induced by anterior cruciate ligament transections. Moreover, urolithin B inhibits the activation of the NF-κB pathway by reducing the phosphorylation of Iκb-α and the nuclear translocation of P65. In summary, urolithin B significantly inhibits inflammation and alleviates osteoarthritis. Hence, urolithin B can be considered a potential agent suitable for the effective treatment of osteoarthritis in the future.

The protective effect of Ergolide in osteoarthritis: In vitro and in vivo studies

Osteoarthritis (OA), a prevalent degenerative condition, occurs due to the deterioration of joint tissues and cells. Consequently, safeguarding chondrocytes against damage caused by inflammation is an area of future research emphasis. There is growing evidence that Ergolide (ERG) has multiple biological functions. Nevertheless, it is still uncertain whether it can hinder the advancement of OA. In this study, we investigate the ERG's potential to reduce inflammation and protect cartilage. ERG treatment in vitro effectively inhibited the excessive production of pro-inflammatory substances, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-α (TNF-α), leading to their complete suppression. Furthermore, ERG suppressed the production of matrix-degrading enzymes (ADAMTS-5) and matrix metalloproteinase 13 (MMP13), consequently impeding the breakdown of extracellular matrix (ECM) and restraining the synthesis of collagenase II and Aggrecan. Through the P38/MAPK pathway, we discovered that ERG hinders the activation of NF-κB in chondrocytes induced by IL-1β. The protective effect of ERG was enhanced by the p38 MAPK inhibitor SB203580. In vivo, ERG further demonstrated protective effects on cartilage in animal models of DMM. In conclusion, the study has discovered that ERG exhibits innovative therapeutic potential in the context of OA.

Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing.

We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR-2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured via gelatin zymography, fluorometric assay, and immunohistochemistry. APC accelerated wound healing in WT mice, but had a negligible effect in PAR-2 KO mice. APC-stimulated murine cutaneous wound healing was associated with the differential and temporal production of MMP-2 and MMP-9, with the latter peaking on day 1 and the former on day 6. Inhibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity by 25~50%, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR-2.

Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype

Background: Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD. Methods: The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80 –/– ) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80 fl/fl SM22α Cre + ) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80 –/– mice were used to evaluate the effect of CCDC80 deficiency on this pathway. Results: CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80 – / – mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p &lt; 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80 –/– mice (8.3% vs. 87.5%, p &lt; 0.05) and CCDC80 fl/fl SM22α Cre + mice (12.5% vs. 80%, p &lt; 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p &lt; 0.05) in CCDC80 knockout mice. Conclusion: CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.

Cyanidin‐3‐galactoside from Aronia melanocarpa ameliorates PM10‐induced pulmonary inflammation by promoting PINK1/Parkin signaling pathway‐mediated alveolar macrophage mitophagy

AbstractAronia melanocarpa is rich in anthocyanin, among which cyanidin‐3‐galactoside (C3G) is the most abundant. Here, we established an experimental model of mice and alveolar macrophage cell line MH‐S exposed to PM10, and C3G was administered to explore the underlying mechanism of C3G exerting protective effects on PM10‐induced lung inflammation. The results showed C3G alleviated PM10‐induced lung inflammation by reducing matrix metalloproteinases production at both gene and protein levels as well as pro‐inflammatory cytokine levels. Autophagy was activated in PM10‐injured alveolar macrophages (AMs), and C3G promoted autophagy indicated by LC3, BECN1, Atg5, Bcl‐2, and P62 expression, and C3G further resisted PM10‐induced AMs apoptosis. Besides, C3G could promote Pink1/Parkin‐mediated mitochondrial autophagy of AMs to alleviate the overexpression of mitochondrial reactive oxygen species (ROS) so that maintain mitochondrial membrane potential and ATP productions to restrict the distribution of Cyt‐c and further reduce the increasing of caspase 3/7 activity. Therefore, C3G enhanced the clearance of PM10‐damaged mitochondria by promoting AMs mitophagy, thereby reducing the activation of mitochondria‐dependent apoptosis pathway and the production of excess ROS, which reduced AMs apoptosis and secretion of pro‐inflammatory factors to ameliorate PM10‐induced pulmonary inflammation, suggesting that C3G may be as a functional food ingredient with the potential to improve lung health.

Mannan-binding lectin ameliorates renal fibrosis by suppressing macrophage-to-myofibroblast transition

Mannan-binding lectin (MBL) is a pattern-recognition molecule that plays a crucial role in innate immunity. MBL deficiency correlates with an increased risk of chronic kidney disease (CKD). However, the molecular mechanisms are not fully defined. Here, we established a CKD model in wild-type (WT) and MBL-deficient (MBL−/−) mice via unilateral ureteral obstruction (UUO). The result showed that MBL deficiency aggravated the pathogenesis of renal fibrosis in CKD mice. Strikingly, the in vivo macrophage depletion investigation revealed that macrophages play an essential role in the MBL-mediated suppression of renal fibrosis. We found that MBL limited the progression of macrophage-to-myofibroblast transition (MMT) in kidney tissues of UUO mice. Further in vitro study showed that MBL−/− macrophages exhibited significantly increased levels of fibrotic-related molecules compared with WT cells upon transforming growth factor beta (TGF-β) stimulation. We demonstrated that MBL inhibited the MMT process by suppressing the production of matrix metalloproteinase 9 (MMP-9) and activation of Akt signaling. In summary, our study revealed an expected role of MBL on macrophage transition during renal fibrosis, thus offering new insight into the potential of MBL as a therapeutic target for CKD.

Protective effect of the brown seaweed Padina boryana against UVB-induced photoaging in vitro in skin cells and in vivo in zebrafish

The ethanol extract of Padina boryana (PB-EtOH) containing phlorotannin effectively inhibits oxidative stress and melanin synthesis, suggesting the potential use of PB-EtOH in the cosmetics industry. To further investigate the cosmetic effects of PB-EtOH, its photoprotective effects against ultraviolet (UV) irradiation was investigated. The results displayed that PB-EtOH remarkably improved cell viability by suppressing the apoptosis via cleaning the intracellular reactive oxygen species (ROS) in UVB-exposed human keratinocytes. In addition, PB-EtOH effectively suppressed oxidative stress, increased collagen synthesis, and reduced the matrix metalloproteinase production in UVB-exposed human dermal fibroblasts in a concentration-dependent manner. Furthermore, the in vivo anti-photoaging effect was determined using the zebrafish model. The results displayed that PB-EtOH remarkably attenuated UVB-stimulated photodamage. The photoprotective effect was displays in reducing the levels of ROS, nitric oxide, lipid peroxidation, and cell death. These results demonstrate that PB-EtOH possesses anti-photoaging effects and suggest that PB-EtOH may be an ideal ingredient to develop a skincare product in the cosmetic industry.

Immunomodulatory effect of Red Moringa oleifera Leaves Fermentation Extract on Il-21 And Il-22 Expressions in Balb/C Mice Exposed to Salmonella typhi

Interleukin-21(IL-21) and interleukin-22(IL-22) expressions in the substantial intestine increase when inflammation occurs. They can also induce the production of pro-inflammatory cytokines and Matrix Metallo Proteinases (MMP) in subepithelial fibroblasts. To evaluate at IL-21 and IL-22 expressions in BALB/c mice after administering red M. oleifera leaf fermented extracts exposed to Salmonella typhi. The expression of IL-21 and IL-22 were evaluated for immunomodulatory effect was analyzed by flowcytometer. Data were analyzed by one-way ANOVA and continued with the Tukey test (p&lt;0.05). The results showed that the fermented extract of red M. oleifera leaves could act as an immunosuppressor characterized by decreased levels of IL-21 and IL-22 both on CD4 T and CD8 T cells in mice injected with Salmonella typhi ranging from 14 mg/Kg BW to 42 mg/Kg BW and Pyrex analysis explains that the cathecin compound has the same active side as 8MR in forming bonds with MMP-9. The results of this study provide is the fermented extract of red M. oleifera leaves decreasing the expression of CD4+IL21+, CD8+IL21+ and CD4+IL22+, CD8+IL22+ through inhibition of MMP-9

Integrin-dependent recruitment of Src to ROS-producing endosomes in osteoarthritic cartilage.

Fibronectin (FN) fragments stimulate catabolic signaling, and, by binding to integrins, they induce chondrocytes to increase the production of matrix metalloproteinases, including MMP-13. In this issue of Science Signaling, Miao etal. reveal that internalization of a FN fragment, but not intact FN, by α5β1 integrin results in the formation of ROS-producing endosomes (redoxosomes) through which chondrocytes detect and respond to damaged matrix by producing more MMP-13.