[Corrigendum] BMP­6 inhibits the metastasis of MDA­MB­231 breast cancer cells by regulating MMP­1 expression.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that the pair of data panels shown for the invasion experiments in Fig. 2D on p. 1826 were strikingly similar to the 'Control' data panels shown for the Transwell assay experiments in Fig. 5C on p. 1829. After having re­examined their original data files, the authors realized that Fig. 5C had been inadvertently assembled incorrectly. The revised version of Fig. 5, now featuring the correct data for the '231­control/Control' and '231­BMP­6/Control' experiments in Fig. 5C, is shown below. Note that the corrections made to this figure do not affect the overall conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 35: 1823­1830, 2016; DOI: 10.3892/or.2015.4540].

Oncostatin M promotes epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Oncostatin M (OSM) may be involved in the promotion of mucosal epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) by inducing matrix metalloproteinase (MMP) -1 and -7. The aim was to evaluate the roles and mechanisms of action of OSM on MMP-1 and -7 synthesis from nasal epithelial cells (NECs). METHODS: OSM, OSM receptor (OSMR), MMP-1 and -7 expression was evaluated in nasal mucosa or primary NECs from scrapings by quantitative polymerase chain reaction (qPCR), immunofluorescence and immunohistochemistry. OSM and other cytokines were used to stimulate air-liquid interface (ALI) cultured NECs. qPCR, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to evaluate the expression of OSMR, MMP-1, -7 and occludin in NECs. RESULTS: Elevated levels of OSMRß, MMP-1 and -7 were found in the tissues and scraped NECs of Eos CRSwNP in comparison to them obtained from the inferior turbinate (IT) and control subjects. The levels of OSM and OSMRß mRNA in tissues were positively correlated with the levels of MMP-1 and -7. OSM stimulation of NECs increased the expression of MMP-1 and -7, and the responses were suppressed by a STAT3 inhibitor, and a PI3K inhibitor respectively. In parallel studies, we found that stimulation with OSM disrupted the localization of occludin, a tight junction protein in NECs. The response was suppressed by a pan-MMP inhibitor. CONCLUSION: OSM induces the synthesis and release of MMP-1 and -7 in NECs. Furthermore, MMP-1 and -7 promote mucosal epithelial barrier dysfunction in patients with Eos CRSwNP.

Exploring blood pressure dynamics and oxidative stress markers in an animal model of polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a hormonal disorder characterized by elevated androgen levels, heightened insulin secretion, and dysregulation of luteinizing hormone and follicle-stimulating hormone. This disorder results in metabolic disruptions, while the irregular estrous cycles associated with PCOS impact cellular functions like growth, movement, and alterations in cell adhesion within the tissue matrix. Aim: This study aims to identify the blood tension, serum malondialdehyde (MDA) levels, and serum Metalloproteinase-1 (MMP-1) in rat models of PCOS. The study was conducted using female Wistar rats aged 6 months weighing between 130 and 180 g. Methods: The rats were divided into three treatment groups: negative control, induction of testosterone propionate (TP) at a dose of 100 mg/kg BW IP for 12 days, and induction of estradiol valerate (EV) at a dose of 2 mg/kg BW IP for 2 days. Data were analyzed quantitatively using a one-way analysis of variance followed by a Posthoc Test using the least significant difference with a confidence level of 95%. Results: The research results indicate that the average blood pressure of TP Group and EV Group did not differ significantly from the negative control (p > 0.05). Serum MDA levels were significantly different in the TP Group compared to the negative control (p < 0.05). On the other hand, MMP-1 levels showed no significant difference (p > 0.05) among all the treatment groups. Conclusion: The findings of this study suggest that TP induction in a rat model of PCOS can potentially contribute to oxidative stress and lipid peroxidation, but does not significantly affect blood pressure or serum MMP-1 levels.

Talin2 binds to non-muscle myosin IIa and regulates cell attachment and fibronectin secretion.

Talin2 is localized to large focal adhesions and is indispensable for traction force generation, invadopodium formation, cell invasion as well as metastasis. Talin2 has a higher affinity toward ß-integrin tails than talin1. Moreover, disruption of the talin2-ß-integrin interaction inhibits traction force generation, invadopodium formation and cell invasion, indicating that a strong talin2-ß-integrin interaction is required for talin2 to fulfill these functions. Nevertheless, the role of talin2 in mediation of these processes remains unknown. Here we show that talin2 binds to the N-terminus of non-muscle myosin IIA (NMIIA) through its F3 subdomain. Moreover, talin2 co-localizes with NMIIA at cell edges as well as at some cytoplasmic spots. Talin2 also co-localizes with cortactin, an invadopodium marker. Furthermore, overexpression of NMIIA promoted the talin2 head binding to the ß1-integrin tail, whereas knockdown of NMIIA reduced fibronectin and matrix metalloproteinase secretion as well as inhibited cell attachment on fibronectin-coated substrates. These results suggest that talin2 binds to NMIIA to control the secretion of extracellular matrix proteins and this interaction modulates cell adhesion.

PLEK2 promotes migration and invasion in pancreatic ductal adenocarcinoma by MMP1 through IL-17 pathway.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis primarily due to metastasis. Accumulating evidence suggests that PLEK2 acts as an oncogene in various tumors. This study aimed to investigate the effects of PLEK2 on PDAC. Expression analysis of PLEK2 was conducted using qRT-PCR, Western blot, and immunohistochemistry in PDAC. Wound healing and transwell assays were performed to evaluate the impact of PLEK2 on cell migration and invasion. A xenograft tumor model was employed to assess the in vivo proliferation of PLEK2. Additionally, the downstream pathway of PLEK2 was analyzed through RNA-seq and confirmed by Western blot analysis. The results demonstrated the upregulation of PLEK2 expression in tumor specimens. High PLEK2 expression was significantly associated with poor overall survival and advanced TNM stages. Correlation analyses revealed positive correlations between PLEK2 and TGF-ß, EGFR, and MMP1. Wound healing and transwell assays demonstrated that PLEK2 promoted PDAC cell migration and invasion, potentially through the activation of the epithelial-to-mesenchymal transition process. The in vivo experiment further confirmed that PLEK2 knockdown suppressed tumor growth. RNA-seq analysis revealed PLEK2's regulation of MMP1 and activation of p-ERK and p-STAT3, which were verified by Western blot analysis. Overall, the present study suggests that PLEK2 may play a tumor-promoting role in PDAC. These findings provide valuable insights into the molecular mechanisms of pancreatic cancer and highlight the potential of PLEK2 as a therapeutic target.

The Anti-Metastatic Action of Oxyresveratrol via Suppression of Phosphoryl-ERK/-PKCα-Mediated Sp1/MMP1 Signaling in Human Renal Carcinoma Cells.

Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki-1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p-ERK/Sp1 and p-PKCα/Sp1-mediated MMP1 expression in RCC.

Exploring the wound-healing potential and seasonal chemical variability of the Formosan Callery pear Pyrus calleryana: implications for therapeutic applications.

CONTEXT: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking. OBJECTIVE: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities. MATERIALS AND METHODS: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'-O-ß-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h. RESULTS: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 µM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1). CONCLUSIONS: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.

mRNA vaccination reduces the thrombotic possibility in COVID-19: Inflammation risk estimates.

Thrombosis is a common clinical feature associated with morbidity and mortality in coronavirus disease-2019 (COVID-19) patients. Cytokine storm in COVID-19 increases patients' systemic inflammation, which can cause multiple health consequences. In this work, we aimed to indicate the effect of Pfizer-BioNTech vaccination on the modulation of monocyte chemoattractant protein-3 (MCP-3), matrix metalloproteinase 1 (MMP-1), and tumor necrosis factor-alpha (TNF-α) levels, and other systemic inflammatory biomarkers that associates with COVID-19 severity in patients who suffers from thrombosis consequences. For this purpose, ninety people were collected from Ibn Al-Nafees Hospital and divided into three groups each of which contained 30 people, 15 of them were venous thromboembolism (VTE) positive and the other were VTE negative. The three groups were non-vaccinated COVID-19, vaccinated COVID-19, and control. The levels of MCP-3 and TNF-α were significantly (p < 0.05) increased in vaccinated and non-vaccinated COVID-19 patients regardless of their thrombosis condition, while MMP-1 level was non-significantly (p > 0.05) higher in vaccinated patients compared to control. MCP-3 and TNF-α were correlated positively with D-dimer (r = 0.544 and r = 0.513, respectively) in non-vaccinated patients, while MMP-1 and TNF-α were correlated positively with D-dimer (r = 0.624 and r = 0.575, respectively) in vaccinated patients. The odds ratio of MCP-3 (2.252), MMP-1 (1.062), and TNF-α (1.360) were reduced in vaccinated patients (2.093, 1.022, and 1.301 for MCP-3, MMP-1, and TNF-α respectively). Thus, MCP-3 plays a vital role in COVID-19 pathophysiology, and vaccination can reduce the risk of developing VTE in COVID-19 patients, and improve the inflammatory condition of patients.

Photoprotective activities of Capsosiphon fulvescens in UVB-induced SKH-1 mice and human keratinocytes.

Capsosiphon fulvescens (CF) is a green alga widely consumed in East Asian countries, particularly in Korea. It has a rich composition of vitamins, minerals, dietary fibers, and bioactive compounds, which contribute to its multiple therapeutic properties. Its application ranges from acting as an antioxidant and anti-inflammatory agent to supporting the skin system. Despite these benefits of CF, the effects and mechanisms of action related to photoaging of the skin have not yet been elucidated. To investigate the photoprotective effects of CF against photoaging, both animal (SKH-1 mouse) and cell models (HaCaT cell line) were used in this study. As a result, administering the CF extract over a period of 10 weeks, which included times of Ultraviolet B (UVB) exposure, significantly reduced erythema and various UVB-induced skin changes, such as wrinkle formation, and the thickening of the epidermis and dermis, as well as alterations in the length and depth of wrinkles. Furthermore, our investigation into CF extract's antiwrinkle properties revealed its efficacy in enhancing skin hydration and collagen content, counteracting the collagen depletion and moisture loss induced by UVB radiation. Also, the fact that the levels of p-ERK, p-p38, and p-JNK proteins went down shows that the CF extract might have a controlling effect on the MAPK signaling pathways. Our findings suggest that CF holds significant potential for preventing photoaging, providing a foundation for the development of functional foods or botanical drugs targeting skin aging and related skin disorders. PRACTICAL APPLICATION: This research proved that Capsosiphon fulvescen, a green alga widely consumed in East Asian countries, provides photoprotective activities against UV-induced skin aging. Therefore, Capsosiphon fulvescen can be utilized as functional foods or botanical drugs targeting skin aging and related skin disorders.

Interleukin-24: A molecular mediator of particulate matter's impact on skin aging.

Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.

AGBL4 promotes malignant progression of glioblastoma via modulation of MMP-1 and inflammatory pathways.

Introduction: Glioblastoma multiforme (GBM), the most common primary malignant brain tumor, is notorious for its aggressive growth and dismal prognosis. This study aimed to elucidate the molecular underpinnings of GBM, particularly focusing on the role of AGBL4 and its connection to inflammatory pathways, to discover viable therapeutic targets. Methods: Single-cell sequencing was utilized to examine the expression levels of AGBL4 and functional assays were performed to assess the effects of AGBL4 modulation. Results: Our findings identified the significant upregulation of AGBL4 in GBM, which correlated with adverse clinical outcomes. Functional assays demonstrated that AGBL4 knockdown inhibited GBM cell proliferation, migration, and invasion and influenced inflammatory response pathways, while AGBL4 overexpression promoted these activities. Further investigation revealed that AGBL4 exerted its oncogenic effects through modulation of MMP-1, establishing a novel regulatory axis critical for GBM progression and inflammation. Discussion: Both AGBL4 and MMP-1 may be pivotal molecular targets, offering new avenues for targeted therapy in GBM management.

Delving into Matrix Metalloproteinase-1 (MMP-1) and its Significance in Periodontal Diseases.

Matrix metalloproteinase-1 (MMP-1) plays a pivotal role in the pathogenesis of periodontal diseases, particularly periodontitis, by virtue of its collagenolytic activity targeting collagen type I, the primary component of periodontal tissues. This review abstract elucidates the intricate involvement of MMP-1 in periodontal tissue homeostasis and its dysregulation in disease states. Elevated MMP-1 levels, observed in gingival tissues and crevicular fluid of individuals with periodontitis, correlate with the degradation of collagen fibers within the periodontium. This degradation contributes to the detachment of teeth from surrounding tissues and exacerbates alveolar bone resorption, hallmark features of periodontal breakdown. Therapeutically, targeting MMP-1 activity emerges as a promising strategy, prompting ongoing research into MMP inhibitors and host modulation therapies. Understanding MMP-1's nuanced role in periodontal diseases paves the way for personalized treatment approaches and holds promise in reshaping periodontal disease management for improved patient outcomes and periodontal health.

Topical Adipose Mesenchymal Stem cell metabolites regulate the expression of MMP-1, MMP-9, EGF, TGF-ß in oral mucosa ulcer rat model.

Objective: Matrix metalloproteinase (MMP-1 and -9), Epidermal Growth Factor (EGF), and Transforming Growth factor (TGF)-ß are expressed in the oral ulcer wound-healing process. The Adipose mesenchymal stem cell metabolites (AdMSCMs) may accelerate wound-healing. This study aimed to investigate the expression of MMP-1, MMP-9, EGF, and TGF-ß in the oral mucosa ulcer rat model treated with topical AdMSCMs. Materials and Methods: Oral ulcer models were created in twenty healthy male Wistar rats (Rattus novergicus) divided into AdMSCMs and control groups. The oral ulcer model was treated topically using AdMSCMs oral gel three times daily for 3 and 7 days. The expression of MMP-1, MMP-9, EGF, TGF-ß was evaluated through histological examination using the immunohistochemistry method. Independent t-test was used to compare the mean of expression of MMP-1, MMP-9, EGF, TGF-ß between control and treatment groups (AdMSCMs), and paired t-test was used to analyze the mean between day 3 and day 7 of each group. Results: A lower expression of MMP-1, MMP-9 in AdMSCMs group and higher expression EGF and TGF-ß in AdMSCMs group compared to the control group in day 3 and day 7. Independent t-test results showed a significant difference in the expression of MMP-1, MMP-9, EGF between the control and AdMSCMs group in day 3 and day 7. Only TGF-ß expression mean difference between day 3 and day 7 showed a significant difference compared to the control groups (p < 0.05). Conclusions: AdMSCMs oral gel may accelerate oral ulcer healing models by reducing the expression MMP-1, MMP-9, and increasing EGF and TGF-ß expressions during the wound-healing process.

Deregulation of Metalloproteinase Expression in Gray Horse Melanoma Ex Vivo and In Vitro.

The ability of human melanoma cells to switch from an epithelial to a mesenchymal phenotype contributes to the metastatic potential of disease. Metalloproteinases (MPs) are crucially involved in this process by promoting the detachment of tumor cells from the primary lesion and their migration to the vasculature. In gray horse melanoma, epithelial-mesenchymal transition (EMT) is poorly understood, prompting us to address MP expression in lesions versus intact skin by transcriptome analyses and the immunofluorescence staining (IF) of gray horse tumor tissue and primary melanoma cells. RNAseq revealed the deregulation of several MPs in gray horse melanoma and, notably, a 125-fold upregulation of matrix metalloproteinase 1 (MMP1) that was further confirmed by RT-qPCR from additional tumor material. The IF staining of melanoma tissue versus intact skin for MMP1 and tumor marker S100 revealed MMP1 expression in all lesions. The co-expression of S100 was observed at different extents, with some tumors scoring S100-negative. The IF staining of primary tumor cells explanted from the tumors for MMP1 showed that the metalloproteinase is uniformly expressed in the cytoplasm of 100% of tumor cells. Overall, the presented data point to MP expression being deregulated in gray horse melanoma, and suggest that MMP1 has an active role in gray horse melanoma by driving EMT-mediated tumor cell dissemination via the degradation of the extracellular matrix. Whilst S100 is considered a reliable tumor marker in human MM, gray horse melanomas do not seem to regularly express this protein.

Differential Gene Analysis of Langerhans Cell Histiocytosis and the Significance of MMP1-Targeted Drug Repositioning.

Langerhans cell histiocytosis (LCH) is a rare condition predominantly affecting young children. Activation of the MAPK pathway has offered key new insights into the pathogenesis of LCH; however, the precise mechanisms underlying its occurrence and development are still far from being completely elucidated. There is still a relapse/reactivation rate in patients with multisystem LCH. Therefore, this study aimed to investigate other potential LCH pathophysiologies and prospective therapeutic targets. The gene expression omnibus (GEO) database was used to retrieve gene expression profiles of LCH (GSE16395). Three distinct types of analyses were performed after identifying the common differentially expressed genes (DEGs) in LCH: hub gene identification, functional annotation, module construction, drug repositioning, and expression analysis via immunohistochemistry (IHC). We identified 417 common DEGs and 50 central hub genes. This functional study highlighted the significance of keratinization, skin development, and inflammation. In addition, we predicted new drug candidates (RS2 drugs targeting matrix metalloprotease1, MMP1) that could be used for LCH treatment. Finally, gene-miRNA and gene-TF networks and immune cell infiltration were analyzed for MMP1-related genes. MMP1 expression levels in LCH tissues were validated by IHC. Our study identified the central communal genes and novel drug candidates. These shared pathways and hub genes offer new perspectives on future mechanisms of action and therapeutic targets.

Irbesartan mitigates the impact of cyclophosphamide-induced acute neurotoxicity in rats: Shedding highlights on NLRP3 inflammasome/CASP-1 pathway-driven immunomodulation.

IIrbesartan (IRB), an angiotensin II type 1 receptor (AT1R) antagonist, has been widely employed in the medical field for its effectiveness in managing hypertension. However, there have been no documented investigations regarding the immunostimulatory properties of IRB. To address this gap, this study has been performed to assess the neuroprotective impact of IRB as an immunostimulatory agent in mitigating acute neurotoxicity induced by cyclophosphamide (CYP) in rats. mRNA levels of nuclear factor erythroid 2 (Nrf-2), interleukin (IL)-18, IL-1ß, and MMP-1 have been assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) has been evaluated to assess the oxidative stress. Additionally, macrophage inflammatory protein 2 (MIP2) has been evaluated using enzyme-linked immunosorbent assay (ELISA). Western blotting has been used to investigate the protein expression of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 (CASP-1), along with an assessment of histopathological changes. Administration of IRB protected against oxidative stress by augmenting the levels of GSH and SOD as well as reducing MDA level. Also, administration of IRB led to a diminishment in the brain levels of MIP2 and MMP1. Furthermore, it led to a suppression of IL-1ß and IL-18 levels, which are correlated with a reduction in the abundance of NLRP3 and subsequently CASP-1. This study provides new insights into the immunomodulatory effects of IRB in the context of CYP-induced acute neurotoxicity. Specifically, IRB exerts its effects by reducing oxidative stress, neuroinflammation, inhibiting chemokine recruitment, and mitigating neuronal degeneration through the modulation of immune markers. Therefore, it can be inferred that the use of IRB as an immunomodulator has the potential to effectively mitigate immune disorders associated with inflammation.

Rosarugosides A and D from Rosa rugosa Flower Buds: Their Potential Anti-Skin-Aging Effects in TNF-α-Induced Human Dermal Fibroblasts.

This present study investigated the anti-skin-aging properties of Rosa rugosa. Initially, phenolic compounds were isolated from a hot water extract of Rosa rugosa's flower buds. Through repeated chromatography (column chromatography, MPLC, and prep HPLC), we identified nine phenolic compounds (1-9), including a previously undescribed depside, rosarugoside D (1). The chemical structure of 1 was elucidated via NMR, HR-MS, UV, and hydrolysis. Next, in order to identify bioactive compounds that are effective against TNF-α-induced NHDF cells, we measured intracellular ROS production in samples treated with each of the isolated compounds (1-9). All isolates reduced the level of ROS at a concentration of 10 µM. Particularly, two depsides-rosarugosides A and D (2 and 1)-significantly inhibited ROS expression in TNF-α-induced NHDFs compared to the other phenolic compounds. Subsequently, the production of MMP-1 and procollagen type Ι α1 by these two depsides was examined. Remarkably, rosarugoside A (2) significantly decreased MMP-1 secretion at all concentrations. In contrast, rosarugoside D (1) regulated the expression of procollagen type Ι α1. These findings collectively suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), hold significant potential for protecting against aging and skin damage. Overall, these findings suggest that Rosa rugosa extracts and their isolated compounds, rosarugosides A (2) and D (1), have the potential to prevent and protect against aging and skin damage, although more specific quantitative analysis is needed.

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis.

Osteosarcoma is a malignant bone tumor affecting adolescents and children. No effective treatment is currently available. Asiatic acid (AA), a triterpenoid compound found in Centella asiatica, possesses anti-tumor, anti-inflammatory, and anti-oxidant properties in various types of tumor cells. This study aims to determine whether AA exerts antitumor effects in human osteosarcoma cells. Our results indicate that AA does not influence the viability, proliferative rate, or cell cycle phase of human osteosarcoma cells under non-toxic conditions. AA suppressed osteosarcoma cell migration and invasion by down-regulating matrix metalloproteinase 1 (MMP1) expression. Data in the TNMplot database suggested MMP1 expression was higher in osteosarcoma than in normal tissues, with associated clinical significance observed in osteosarcoma patients. Overexpression of MMP1 in osteosarcoma cells reversed the AA-induced suppression of cell migration and invasion. AA treatment decreased the expression of specificity protein 1 (Sp1), while Sp1 overexpression abolished the effect of AA on MMP1 expression and cell migration and invasion. AA inhibited AKT phosphorylation, and treatment with a PI3K inhibitor (wortmannin) increased the anti-invasive effect of AA on osteosarcoma cells via the p-AKT/Sp1/MMP1 axis. Thus, AA exhibits the potential for use as an anticancer drug against human osteosarcoma.

Protective effect of mixture of Acanthopanax sessiliflorum and Chaenomeles sinensis against ultraviolet B-induced photodamage in human fibroblast and hairless mouse.

Skin photoaging, characterized by collagen degradation and upregulation of matrix metalloproteinases (MMPs), is a major concern caused by UVB irradiation. In this study, we investigated the potential of Acanthopanax sessiliflorum extract (ASE) and Chaenomeles sinensis (CSE) extracts to mitigate the effects of UVB-induced photodamage in human fibroblast and hairless mice. Water extracts of AS (ASE) and CS (CSE) were found to inhibit the expression of MMP-1/-3 in vitro. Furthermore, the extract of mixture of AS and CS (ACE) showed more potent inhibitor effect, as compared to ASE and CSE. In UVB-irradiated hairless mice, oral administration of ACE effectively reduced wrinkle formation, skin roughness, and epidermal thickness while promoting the deposition of collagenous fibers. These results indicate that ACE has the potential to protect against skin photoaging by restoring the impaired skin via downregulation of MMP-1/-3 expression and secretion. Our findings highlight the therapeutic potential of ACE in mitigating skin photoaging. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01462-3.

MMP1, IL-1ß, sTNFR-1, and IL-6 are prognostic factors for patients with unresectable or metastatic renal cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Few studies have reported reliable prognostic factors for immune checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC). Therefore, we investigated prognostic factors in patients treated with ICIs for unresectable or metastatic RCC. METHODS: We included 43 patients who received ICI treatment for RCC between January 2018 and October 2021. Blood samples were drawn before treatment, and 73 soluble factors in the plasma were analyzed using a bead-based multiplex assay. We examined factors associated with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAE) using the Chi-squared test, Kaplan-Meier method, and the COX proportional hazards model. RESULTS: Patients exhibited a median PFS and OS of 212 and 783 days, respectively. Significant differences in both PFS and OS were observed for MMP1 (PFS, p < 0.001; OS, p = 0.003), IL-1ß (PFS, p = 0.021; OS, p = 0.008), sTNFR-1 (PFS, p = 0.017; OS, p = 0.005), and IL-6 (PFS, p = 0.004; OS, p < 0.001). Multivariate analysis revealed significant differences in PFS for MMP1 (hazard ratio [HR] 5.305, 95% confidence interval [CI], 1.648-17.082; p = 0.005) and OS for IL-6 (HR 23.876, 95% CI, 3.426-166.386; p = 0.001). Moreover, 26 patients experienced irAE, leading to ICI discontinuation or withdrawal. MMP1 was significantly associated with irAE (p = 0.039). CONCLUSION: MMP1 may be associated with severe irAE, and MMP1, IL-1ß, sTNFR-1, and IL-6 could serve as prognostic factors in unresectable or metastatic RCC treated with ICIs. MMP1 and IL-6 were independent predictors of PFS and OS, respectively. Thus, inhibiting these soluble factors may be promising for enhancing antitumor responses in patients with RCC treated with ICIs.