Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.

Serum vitamin D concentration is inversely associated with matrix metalloproteinase-9 level in periodontal diseases.

BACKGROUND: The aim of this study was to investigate the potential association between vitamin D deficiency and matrix metalloproteinase-9 (MMP-9) levels in gingival crevicular fluid (GCF) across various periodontal health and disease statuses. METHODS: A total of 200 volunteers were divided into two groups according to serum vitamin D concentration (25(OH)D < 10 ng/mL and 25(OH)D ≥ 10 ng/mL). Periodontal health status was determined based on a full-mouth periodontal examination and radiographic evaluation. Participants in both groups were categorized according to periodontal diagnoses, encompassing periodontal health, gingivitis, and periodontitis. Following sampling, the MMP-9 levels in GCF were determined by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The GCF MMP-9 levels were found to be higher in individuals with serum 25(OH)D < 10 ng/mL, in both the healthy and gingivitis and periodontitis groups, compared to those with 25(OH)D ≥ 10 ng/mL. Nevertheless, a statistically significant distinction was observed exclusively within the gingivitis and periodontitis groups. Correlation analysis and robust regression analyses provided additional evidence supporting the predictive role of periodontal disease status and vitamin D concentration in local MMP-9 levels. These associations remained significant after adjusting for age and sex in robust regression analysis (p = 0.002). Furthermore, the inclusion of periodontal clinical parameters in the regression analysis revealed notable associations of clinical attachment loss with local MMP-9 levels, along with periodontal disease status and serum vitamin D concentration (p < 0.001). CONCLUSION: The findings of our study suggest a potential mechanistic relationship between serum vitamin D levels and periodontitis. PLAIN LANGUAGE SUMMARY: Vitamin D deficiency is a widespread issue globally due to urban living, less outdoor time, seasonal changes, aging, and sunscreen use, leading to inadequate sun exposure. Low vitamin D levels are linked to several health problems, including hypertension, diabetes, heart diseases, and periodontal diseases, which affect the gums and bones around teeth and can cause tooth loss if untreated. Although the link between vitamin D and periodontal disease is unclear, it may involve the enzyme matrix metalloproteinase-9 (MMP-9). Our study examined 200 people, dividing them into two groups based on vitamin D levels. We assessed their gum health and measured MMP-9 levels in their gingival crevicular fluid, a liquid that seeps out from the tiny space between gums and teeth. We found that people with lower vitamin D levels had higher MMP-9 levels, especially those with gum disease. Our analysis showed that both vitamin D levels and gum health significantly impact MMP-9 levels, with gum health being the more influential factor. Maintaining good gum health and adequate vitamin D levels is crucial for managing MMP-9, an enzyme critical for tissue remodeling during healing and inflammation. However, excessive MMP may rapidly destroy periodontal tissues.

Liquiritin ameliorates painful diabetic neuropathy in SD rats by inhibiting NLRP3-MMP-9-mediated reversal of aquaporin-4 polarity in the glymphatic system.

Background: Despite advancements in diabetes treatment, the management of Painful Diabetic Neuropathy (PDN) remains challenging. Our previous research indicated a significant correlation between the expression and distribution of Aquaporin-4 (AQP4) in the spinal glymphatic system and PDN. However, the potential role and mechanism of liquiritin in PDN treatment remain uncertain. Methods: This study established a rat model of PDN using a combination of low-dose Streptozotocin (STZ) and a high-fat, high-sugar diet. Rats were treated with liquiritin and MCC950 (an NLRP3 inhibitor). We monitored fasting blood glucose, body weight, and mechanical allodynia periodically. The glymphatic system's clearance function was evaluated using Magnetic Resonance Imaging (MRI), and changes in proteins including NLRP3, MMP-9, and AQP4 were detected through immunofluorescence and Western blot techniques. Results: The rats with painful diabetic neuropathy (PDN) demonstrated several physiological changes, including heightened mechanical allodynia, compromised clearance function within the spinal glymphatic system, altered distribution of AQP4, increased count of activated astrocytes, elevated expression levels of NLRP3 and MMP-9, and decreased expression of AQP4. However, following treatment with liquiritin and MCC950, these rats exhibited notable improvements. Conclusion: Liquiritin may promote the restoration of AQP4 polarity by inhibiting NLRP3 and MMP-9, thereby enhancing the clearance functions of the spinal cord glymphatic system in PDN rats, alleviating the progression of PDN.

Evaluation of the effect of taurine on the matrix metalloproteinase-9 and the expression changes of miRNA-21 and miRNA-146a in SH-SY5Y cell line.

OBJECTIVES: Alzheimer's disease (AD), a brain disorder, is the leading cause of dementia among older adults. Taurine, an amino acid abundantly present in the brain, and shows potential neuroprotective properties. Therefore, we investigated the effects of taurine on Matrix Metalloproteinase-9 (MMP-9) levels and the expression changes of miRNA-21 and miRNA-146a in the SH-SY5Y cell line. METHODS: Taurine's impact on the SH-SY5Y cell line was evaluated via the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. MMP-9 levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while the expression of miRNA-21 and miRNA-146a genes was assessed through Real-Time PCR analysis. RESULTS: The MTT assay revealed no toxic effects on SH-SY5Y cells with increasing concentrations of taurine. Analysis of gene expression indicated a rise in miRNA-21 expression and a decline in miRNA-146 expression with increasing taurine concentration, with the most notable change observed at 1 mg/mL taurine (p<0.001). ELISA results demonstrated a significant increase in MMP-9 levels in the SH-SY5Y cell line treated with 1 mg/mL taurine compared to the untreated group (p<0.001). CONCLUSIONS: Our study revealed that taurine can alter the expression of miRNA-146a and miRNA-21. In conclusion, taurine therapy presents promising therapeutic avenues for treating AD or mitigating severe symptoms. Nonetheless, further research is necessary to comprehensively grasp the precise mechanisms at play.

L48H37, a curcumin analog, suppresses matrix metalloproteinase-9 expression and activity to hamper nasopharyngeal cancer cell migration.

OBJECTIVE: Metastatic disease is a major issue of treatment failure in nasopharyngeal carcinoma (NPC) patients and often linked to high mortality. L48H37, a synthetic analog of curcumin with augmented bioavailability over its parent compound, has demonstrated several oncostatic characteristics. This study was aimed to explore the anti-metastatic effect of L48H37 on NPC cancer cells and its underlying mechanism. METHODS: Cell viability was evaluated using MTT assay. Regulation of signaling pathways was elucidated by immunoblotting, and specific kinase inhibitors. RESULTS: In this study, we showed that L48H37 suppressed TPA-stimulated invasive and migratory capacities of NPC cell lines and gave rise to very little cytotoxic responses. Such anti-cancer effect of L48H37 was accompanied with attenuated expression levels and enzymatic activities of matrix metalloproteinase-9 (MMP-9), a pivotal mediator of metastatic processes. In addition, L48H37 interfered with TPA-induced JNK activation, and the treatment of L48H37 combined with a JNK antagonist demonstrated a synergistic effect on restraining TPA-stimulated MMP-9 activity and migration events in NPC cells. CONCLUSIONS: Our results revealed that L48H37 impeded the invasive potential of NPC cells via impairment of MMP-9 function and abundance, highlighting possible complementary therapies using curcumin or its effective analogs to manage NPC dissemination.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.

Turmeric extract alleviates airway inflammation via oxidative stress-driven MAPKs/MMPs pathway.

Turmeric (Curcuma longa L.) extract (CLE) has been shown to elicit several pharmacological properties and is widely used in Asian traditional medicine. Herein, we assessed the impact of CLE on airway inflammation in BALB/c mice and A549 cells to clarify the underlying mechanism. An asthmatic mouse model was established by administering ovalbumin (OVA). CLE (100 or 300 mg/kg/day) was orally administered daily from days 18 to 23, with dexamethasone (3 mg/kg/day) used as the positive control. Human airway epithelial cells, A549, were stimulated using recombinant tumor necrosis factor-α. The CLE100 and CLE400 groups exhibited a significant downregulation in eosinophil counts, cytokine levels, and immunoglobulin-E levels. Moreover, CLE administration dose-dependently suppressed oxidative stress and airway inflammation in the lung tissue. CLE administration inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expression and activity of matrix metalloproteinase (MMP)-9. In vitro, CLE treatment reduced mRNA levels of proinflammatory cytokines, MAPK phosphorylation, and the expression and activity of MMP-2 and MMP-9. Additionally, 50 µg/mL CLE and 2.5 µg/mL curcumin showed similar anti-inflammatory effects. Collectively, our findings revealed that CLE could suppress airway inflammation in asthmatic mice and A549 cells via oxidative stress-driven MAPK/MMPs signaling, suggesting that CLE could be developed as a potential treatment option for patients with asthma.

Unveiling the bioinformatic genes and their involved regulatory mechanisms in type 2 diabetes combined with osteoarthritis.

Background: Type 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA. Methods: T2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking. Results: In this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA. Conclusion: This study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition.

Investigating salivary matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in fixed orthodontic-induced gingival enlargement.

Background: Gingival enlargement (GE) is a common clinical observation among orthodontic patients, yet its underlying causes remain unclear. This study aims to investigate the potential involvement of salivary matrix metalloproteinase (MMP)-2 and MMP-9 activity in orthodontic-induced GE. Materials and Methods: In this case-control study, we enrolled 50 subjects, including 25 individuals with GE and 25 without. The participants, aged 10-35 years, were in the 4th or 5th month of their orthodontic treatment. Comprehensive clinical assessments, encompassing plaque index, gingival index, and GE score were performed, and saliva samples were subjected to gelatin zymography to assess enzyme activity. Statistical analysis, including the Chi-square test for age distribution, independent samples t-test for age comparison between study groups, Mann-Whitney U test for MMP activity comparison, and Wilcoxon signed-rank test for comparison of data from the 4th to 5th months of treatment, was performed using SPSS version 23.0, with a significance level set at 0.05. Results: MMP-2 activity was undetectable in the zymograms. In the 4th month of treatment, MMP-9 activity was more prominent in the case group, though this disparity did not reach statistical significance in the 5th month. Furthermore, MMP-9 activity did not exhibit a correlation with the GE score. Conclusion: The activity of MMP-9 in the saliva of orthodontic patients with GE increases during the 4th month of treatment, but no correlation exists with the degree of GE.

Matrix Metalloproteinase 9 (MMP-9) and Interleukin-8 (IL-8) in Gingival Crevicular Fluid after Minimally Invasive Periodontal Surgery with or without Er:YAG and Nd:YAG Laser Application.

BACKGROUND: This study aimed to evaluate alterations in the concentrations of matrix metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) within gingival crevicular fluid (GCF) extracted from the intrabony periodontal defect site before and after minimally invasive regenerative surgery, with or without supplemental laser application. The surgical procedure was performed using the modified minimally invasive surgical technique (M-MIST). METHODS: Thirty-eight patients, each presenting with a single vertical defect, were randomly assigned to either the test (M-MIST + Er:YAG + Nd:YAG) or the control group (M-MIST). IL-8 and MMP-9 levels (primary outcomes of the study) were assessed prior to therapy, after 2 and 4 weeks, and 6 months following the surgical procedure by means of dedicated ELISA kits. RESULTS: Both procedures were clinically effective as evidenced by probing depth (PD) reduction and clinical attachment level (CAL) gain at the 6-month follow-up. No statistical differences were observed in the levels of MMP-9 and IL-8 between the groups at any time point assessed. The changes in the level of MMP-9 and IL-8 over time were not statistically significant in any group. IL-8 was positively correlated with MMP-9 in the control group throughout the study and in the test group 2 weeks and 6 months post-op. CONCLUSIONS: Within the limitations of this study, the additional application of Er:YAG + Nd:YAG lasers alongside the M-MIST procedure did not enhance the clinical and biochemical treatment outcomes compared to M-MIST alone.

Prognostic value of matrix metalloproteinase-2 protein and matrix metalloproteinase-9 protein in colorectal cancer: a meta-analysis.

INTRODUCTION: Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are critical components of the extracellular matrix (ECM) in colorectal cancer (CRC). We aimed to evaluate the prognostic value of MMP-2 and MMP-9 in patients with CRC. METHODS: We performed a meta-analysis of cohort studies with available data on the effect of MMP-2 and MMP-9 expression on both disease-free survival (DFS) and overall survival (OS) by the risk ratios (RRs) with their 95% confidence intervals (CIs). Studies were subgrouped based on the different tissue types, including cancer tissue and normal tissue, and the subgroup effect of MMP expression in different tissues was analyzed through meta-regression. To ensure the quality and reduce the risk of bias, the Newcastle‒Ottawa Scale (NOS) was used to assess the included studies. A sensitivity analysis was randomly performed to assess the potential impact of each study on our results. RESULTS: Eighteen trials were selected (Table 1) and included a total of 3944 patients. According to our primary meta-analysis, the expression of MMP-2 was significantly associated with a decrease in OS (RR = 1.75, 95% CI = 1.34 to 2.29, P < 0.001) and DFS (RR = 2.62, 95% CI = 1.25 to 5.49, P < 0.001), and the expression of MMP-9 was not significantly associated with a decrease in OS (RR = 1.48, 95% CI = 0.97 to 2.24, P = 0.069) or DFS (RR = 1.60, 95% CI = 0.87 to 2.94, P = 0.133). According to the subgroup analysis of MMPs in different tissues, high MMP-2 expression in cancer tissue (RR = 1.90, 95% CI = 1.29 to 2.79) and normal tissue (RR = 1.59, 95% CI = 1.17 to 2.17) were significant indicators of poor OS. High MMP-2 expression in cancer tissue was significant indicator of poor DFS (RR = 2.12, 95% CI = 1.09 to 4.11). MMP-9 expression was also associated with poor OS (RR = 1.40, 95% CI = 0.85 to 2.29), but the difference in OS between the high and low expression groups was not statistically significant. CONCLUSIONS: High MMP-2 expression, especially in cancer tissue, is significantly associated with both poor DFS and poor OS in patients with CRC. High MMP-9 expression tended to indicate a poor prognosis of CRC but the correlation was not significant.

Microbiological and Salivary Biomarkers Successfully Predict Site-Specific and Whole-Mouth Outcomes of Nonsurgical Periodontal Treatment.

Background/Objectives: Nonsurgical periodontal treatment (NSPT) is the gold-standard technique for treating periodontitis. However, an individual's susceptibility or the inadequate removal of subgingival biofilms could lead to unfavorable responses to NSPT. This study aimed to assess the potential of salivary and microbiological biomarkers in predicting the site-specific and whole-mouth outcomes of NSPT. Methods: A total of 68 periodontitis patients exhibiting 1111 periodontal pockets 4 to 6 mm in depth completed the active phase of periodontal treatment. Clinical periodontal parameters, saliva, and subgingival biofilm samples were collected from each patient at baseline and three months after NSPT. A quantitative PCR assay was used to detect the presence of Fusobaterium nucleatum and Porphyromonas gingivalis in the biofilm samples. Salivary biomarkers including matrix metalloproteinase (MMP)-9, glutathione S-transferase (GST), and Annexin-1 were assayed both qualitatively (Western blot analysis) and quantitively (ELISA). Results: NSPT yielded significant improvements in all clinical parameters, including a reduction in bacterial load and decreased levels of MMP-9 together with increased concentrations of GST and Annexin-1. The binary logistic regression suggested that the overall accuracy of P. gingivalis identification, probing pocket depth, and interproximal sites was 71.1% in predicting successful site-specific outcomes. The salivary biomarker model yielded an overall accuracy of 79.4% in predicting whole-mouth outcomes following NSPT. Conclusions: At baseline, the presence of shallow periodontal pockets at interdental locations with a lower abundance of P. gingivalis is predictive of a favorable response to NSPT at the site level. Decreased salivary MMP-9 associated with increased GST and Annexin-1 levels can predict successful whole-mouth outcomes following NSPT.

Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes.

OBJECTIVE: To explore whether the regulation of matrix metalloproteinase 9 (MMP-9)/ tissue inhibitors of MMPs (TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture (EA) protects blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) rat model. METHODS: Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA (MEA) group, and the MCAO + EA + HAT inhibitor (HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui (GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation (ChIP). RESULTS: Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. CONCLUSION: EA treatment at Baihui (GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer.

BACKGROUND: Prostate cancer (PC) is one of the most common malignant tumors in men, and bone metastasis is one of its common complications, which seriously affects the quality of life and prognosis of patients. AIM: To investigate the diagnostic value of technetium-99m-methylene diphosphonate (99mTc-MDP) single photon emission computed tomography (SPECT)/CT imaging combined with the serum prostate-specific antigen (PSA)/free PSA ratio for PC bone metastasis (PCBM). METHODS: One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental (Exp) group, while 30 patients with benign prostatic lesions (BPLs) were recruited as the control (Ctrl) group. All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing. The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM. RESULTS: The difference in general information of the patients was not obvious, showing comparability. The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM, but had great differences in positive predictive value and specificity (P < 0.05). The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs, and patients with PCBM had a much lower PSA/fPSA ratio than those without PC (P < 0.05). The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95% for PCBM. CONCLUSION: The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM, which provides an important reference for clinical practice.

AGEs induce MMP-9 promoter demethylation through the GADD45α-mediated BER pathway to promote breast cancer metastasis in patients with diabetes.

Scientific evidence has linked diabetes to a higher incidence and increased aggressiveness of breast cancer; however, mechanistic studies of the numerous regulators involved in this process are insufficiently thorough. Advanced glycation end products (AGEs) play an important role in the chronic complications of diabetes, but the mechanisms of AGEs in breast cancer are largely unexplored. In this study, we first demonstrate that high AGE levels in breast cancer tissues are associated with the diabetic state and poor patient outcomes. Furthermore, AGEs interact with the receptor for AGEs (RAGE) to promote breast cancer cell migration and invasion. Mechanistically, based on RNA sequencing (RNA-seq) analysis, we reveal that growth arrest and DNA damage gene 45α (GADD45α) is a vital protein upregulated by AGEs through a P53-dependent pathway. Next, GADD45α recruits thymine DNA glycosylase for base excision repair to form the demethylation complex at the promoter region of MMP-9 and enhance MMP-9 transactivation through DNA demethylation. Overall, our results indicate a critical regulatory role of AGEs in patients with breast cancer and diabetes and reveal a novel mechanism of epigenetic modification in promoting breast cancer metastasis.

Chitinase-3-like protein 1, matrix metalloproteinase-9, and monocyte chemoattractant protein-1 as potential biomarkers and treatment targets of adenomyosis.

OBJECTIVE: This study aimed to investigate the levels of chitinase-3-like protein-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), and monocyte chemoattractant protein-1 (MCP-1) in adenomyosis, as compared to normal myometrial tissue. These biomarkers may be useful for determining potential treatment targets. METHODS: This was a correlative, analytical, and observational study with a cross-sectional design. Participants with a diagnosis of moderate-to-severe adenomyosis, as determined through transvaginal ultrasonography and histological examination, and who underwent laparotomy or laparoscopic surgery for the treatment of adenomyosis, were enrolled in the study. Unlike other studies that recruited healthy women as controls, our study used adenomyotic and healthy nonadenomyotic myometria obtained from the same individual. The levels of CHI3L1, MMP-9, and MCP-1 in the biopsy samples were determined using enzyme-linked immunoassay kits, according to the manufacturer's protocol. RESULTS: A highly significant increase in the levels of CHI3L1, MMP-9, and MCP-1 was found in adenomyotic tissues compared to non-adenomyotic tissues (P<0.001). A significant positive correlation was found between CHI3L1 and MMP-9 levels (r=0.463; P=0.008), CHI3L1 and MCP-1 levels (r=0.594; P<0.001), and MCP-1 and MMP-9 levels (r=0.680; P<0.001) in adenomyotic tissues. CONCLUSION: CHI3L1 may play a role in the pathogenesis of adenomyosis via the regulation of the MCP-1 and MMP-9 pathways. Therefore, these molecules may serve as biomarkers and potential therapeutic targets for adenomyosis.

Aversatile MOF as an electrochemical/fluorescence/colorimetric signal probe for the tri-modal detection of MMP-9 secretion in the extracellular matrix to identify the efficacy of chemotherapeutic drugs.

BACKGROUND: MMP-9 plays a crucial role in regulating the degradation of proteins within the extracellular matrix (ECM). This process closely correlates with the occurrence, development, invasion, and metastasis of various tumors, each exhibiting diverse levels of MMP-9 expression. However, the accuracy of detection results using the single-mode method is compromised due to the coexistence of multiple biologically active substances in the ECM. RESULTS: Therefore, in this study, a tri-modal detection system is proposed to obtain more accurate information by cross-verifying the results. Herein, we developed a tri-modal assay using the ZIF-8@Au NPs@S QDs composite as a multifunctional signal probe, decorated with DNA for the specific capture of MMP9. Notably, the probe demonstrated high conductivity, fluorescence response and mimicked enzyme catalytic activity. The capture segments of hybrid DNA specifically bind to MMP9 in the presence of MMP9, causing the signal probe to effortlessly detach the sensor interface onto the sample solution. Consequently, the sensor current performance is weakened, with the colorimetric and fluorescent signals becoming stronger with increasing MMP9 concentration. Notably, the detection range of the tri-modal sensor platform spans over 10 orders of magnitude, verifying notable observations of MMP-9 secretion in four tumor cell lines with chemotherapeutic drugs. Furthermore, the reliability of the detection results can be enhanced by employing pairwise comparative analysis. SIGNIFICANCE: This paper presents an effective strategy for detecting MMP9, which can be utilized for both the assessment of MMP-9 in cell lines and for analyzing the activity and mechanisms involved in various tumors.

Matrix Remodeling Enzymes as Potential Fluid Biomarkers of Neurodegeneration in Alzheimer's Disease.

This study investigated the diagnostic accuracy of plasma biomarkers-specifically, matrix metalloproteinase (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), CD147, and the MMP-/TIMP-1 ratio in patients with Alzheimer's disease (AD) dementia. The research cohort comprised patients diagnosed with probable AD dementia and a control group of cognitively unimpaired (CU) individuals. Neuroradiological assessments included brain magnetic resonance imaging (MRI) following dementia protocols, with subsequent volumetric analysis. Additionally, cerebrospinal fluid (CSF) AD biomarkers were classified using the A/T/N system, and apolipoprotein E (APOE) ε4 carrier status was determined. Findings revealed elevated plasma levels of MMP-9 and TIMP-1 in AD dementia patients compared to CU individuals. Receiver operating characteristic (ROC) curve analysis demonstrated significant differences in the areas under the curve (AUC) for MMP-9 (p < 0.001) and TIMP-1 (p < 0.001). Notably, plasma TIMP-1 levels were significantly lower in APOE ε4+ patients than in APOE ε4- patients (p = 0.041). Furthermore, APOE ε4+ patients exhibited reduced hippocampal volume, particularly in total, right, and left hippocampal measurements. TIMP-1 levels exhibited a positive correlation, while the MMP-9/TIMP-1 ratio showed a negative correlation with hippocampal volume parameters. This study sheds light on the potential use of TIMP-1 as a diagnostic marker and its association with hippocampal changes in AD.

Complement regulatory protein CD46 promotes bladder cancer metastasis through activation of MMP9.

CD46, a transmembrane protein known for protecting cells from complement­mediated damage, is frequently dysregulated in various types of cancer. Its overexpression in bladder cancers safeguards the cancer cells against both complement and antibody­mediated cytotoxicity. The present study explored a new role of CD46 in facilitating cancer cell invasion and metastasis, examining its regulatory effect on matrix metalloproteases (MMPs) and their effect on the metastatic capability of bladder cancer cells. Specifically, CD46 alteration positively influenced MMP9 expression, but not MMP2, in several bladder cancer cell lines. Furthermore, CD46 overexpression triggered phosphorylation of p38 MAPK and protein kinase B (AKT), leading to enhanced activator protein 1 (AP­1) activity via c­Jun upregulation. The inhibition of p38 or AKT pathways attenuated the CD46­induced MMP9 and AP­1 upregulation, indicating that the promotion of MMP9 by CD46 involved activating both p38 MAPK and AKT. Functionally, the upregulation of MMP9 by CD46 translated to increased migratory and invasive capabilities of bladder cancer cells, as well as enhanced in vivo metastasis. Overall, the present study revealed a novel role for CD46 as a metastasis promoter through MMP9 activation in bladder cancers and highlighted the regulatory mechanism of CD46­mediated MMP9 promotion via p38 MAPK and AKT activation.

AHNAK2 Regulates NF-κB/MMP-9 Signaling to Promote Pancreatic Cancer Progression.

Early metastasis of pancreatic cancer (PaC) is a major cause of its high mortality rate. Previous studies have shown that AHNAK2 is involved in the progression of some tumors and is predicted to be an independent prognostic factor for PaC; however, the specific mechanisms through which AHNAK2 regulates PaC remain unclear. In this study, we examined the role of AHNAK2 in PaC and its potential molecular mechanisms. AHNAK2 mRNA and protein expression in PaC tissues and cells were measured using qRT-PCR and western blot analysis. After AHNAK2 knockdown using small interfering RNA, PaC cells were subjected to CCK-8 scratch, and Transwell assays to assess cell proliferation, migration, and invasion, respectively. Furthermore, the validation of the mechanistic pathway was achieved by western blot analysis. AHNAK2 mRNA and protein levels were up-regulated in PaC and silencing AHNAK2 significantly inhibited the proliferation, migration, and invasion of PaC cells. Mechanistically, AHNAK2 knockdown decreased the expression of phosphorylated p65, phosphorylated IκBα, and matrix metalloproteinase-9 (MMP-9), suggesting that activation of the NF-κB/MMP-9 signaling pathway was inhibited. Importantly, activation of NF-κB reversed the effects of AHNAK2 knockdown. Our findings indicate that AHNAK2 promotes PaC progression through the NF-kB/MMP-9 pathway and provides a theoretical basis for targeting AHNAK2 for the treatment of PaC.