Correlation of amniotic fluid inflammatory markers with preterm birth: a meta-analysis.

BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.

A critical influence of HIF-1 on MMP-9 and Galectin-3 in oral lichen planus.

OBJECTIVE: Oral lichen planus carries a risk for malignancy. The pathogenesis of the disease is mediated by various inflammatory mediators. Several mediators could be responsible for the oncogenic behavior in certain cases. Hypoxia-inducible factor-1a (HIF-1), and its possible correlation to Galactin-3 (Gal-3) and matrix metalloproteinase-9 (MMP-9) over expression represents an important indicator for malignant transformation. The investigation of these factors may present evidence-based information on malignant transformation of the disease. SUBJECTS AND METHODS: The study investigated the expression of HIF-1, Gla-3 and MMP-9 in tissue samples of OLP compared to control subjects of un-inflamed gingival overgrowth. 20 biospecimen were allocated in each group. RESULTS: Immunohistochemical findings of OLP showed immunoreactivity for Galectin 3, HIF1a and MMP-9 by most of the epithelial cells. There was a positive correlation between HIF1α and MMP-9, r = 0.9301 (P-value < 0.00001). A positive correlation was detected between Galectin 3 and MMP-9, r = 0.7292 (P-value = 0.000264) between Galectin 3 and HIF1α, r = 0.5893 (P-value = 0.006252). CONCLUSION: These findings confirm the hypothesis that the adaptive pathways to hypoxia as Gal 3 and MMP-9 expressions and their HIF-1 may play a crucial role in carcinogenesis of OLP.

In Vitro Assessment of 4-Acetyl-Antroquinonol B and Erinacine A in Suppressing Breast Cancer-Induced Osteoclastogenesis.

Bone metastasis in metastatic breast cancer commonly results in osteolytic lesions due to osteoclast activity, promoting bone destruction and tumor progression. The bioactive fungal isolates, 4-acetyl-antroquinonol B (4-AAQB) and erinacine A, have diverse pharmacological and biological activities. However, their effects on breast cancer bone metastasis treatment remain unclear. Our study aimed to examine the impact of 4-AAQB or erinacine A on breast cancer metastases in bone. The effects of 4-AAQB and erinacine A on breast cancer-induced osteoclastogenesis, breast cancer migration, production of prometastatic cytokine (TGF-ß) and marker (MMP-9), as well as potential MAPK signaling transductions were assessed. The results revealed that 4-AAQB and erinacine A effectively suppressed breast cancer-induced osteoclastogenesis and migration, and reduced TGF-ß and MMP-9 production via Erk or JNK signaling transductions, specifically in breast cancer cells or in breast cancer cells-induced osteoclasts. Based on these findings, either 4-AAQB or erinacine A showed promise in preventing breast cancer metastases in bone.

Matrix metalloproteinase 9 expression and glioblastoma survival prediction using machine learning on digital pathological images.

This study aimed to apply pathomics to predict Matrix metalloproteinase 9 (MMP9) expression in glioblastoma (GBM) and investigate the underlying molecular mechanisms associated with pathomics. Here, we included 127 GBM patients, 78 of whom were randomly allocated to the training and test cohorts for pathomics modeling. The prognostic significance of MMP9 was assessed using Kaplan-Meier and Cox regression analyses. PyRadiomics was used to extract the features of H&E-stained whole slide images. Feature selection was performed using the maximum relevance and minimum redundancy (mRMR) and recursive feature elimination (RFE) algorithms. Prediction models were created using support vector machines (SVM) and logistic regression (LR). The performance was assessed using ROC analysis, calibration curve assessment, and decision curve analysis. MMP9 expression was elevated in patients with GBM. This was an independent prognostic factor for GBM. Six features were selected for the pathomics model. The area under the curves (AUCs) of the training and test subsets were 0.828 and 0.808, respectively, for the SVM model and 0.778 and 0.754, respectively, for the LR model. The C-index and calibration plots exhibited effective estimation abilities. The pathomics score calculated using the SVM model was highly correlated with overall survival time. These findings indicate that MMP9 plays a crucial role in GBM development and prognosis. Our pathomics model demonstrated high efficacy for predicting MMP9 expression levels and prognosis of patients with GBM.

Reduction in ACE2 expression in peripheral blood mononuclear cells during COVID-19 - implications for post COVID-19 conditions.

BACKGROUND: Severe COVID-19 is uncommon, restricted to 19% of the total population. In response to the first virus wave (alpha variant of SARS-CoV-2), we investigated whether a biomarker indicated severity of disease and, in particular, if variable expression of angiotensin converting enzyme 2 (ACE2) in blood might clarify this difference in risk and of post COVID -19 conditions (PCC). METHODS: The IRB-approved study compared patients hospitalized with severe COVID-19 to healthy controls. Severe infection was defined requiring oxygen or increased oxygen need from baseline at admission with positive COVID-19 PCR. A single blood sample was obtained from patients within a day of admission. ACE2 RNA expression in blood cells was measured by an RT-PCR assay. Plasma ACE1 and ACE2 enzyme activities were quantified by fluorescent peptides. Plasma TIMP-1, PIIINP and MMP-9 antigens were quantified by ELISA. Data were entered into REDCap and analyzed using STATA v 14 and GraphPad Prism v 10. RESULTS: Forty-eight patients and 72 healthy controls were recruited during the pandemic. ACE2 RNA expression in peripheral blood mononuclear cells (PBMC) was rarely detected acutely during severe COVID-19 but common in controls (OR for undetected ACE2: 12.4 [95% CI: 2.62-76.1]). ACE2 RNA expression in PBMC did not determine plasma ACE1 and ACE2 activity, suggesting alternative cell-signaling pathways. Markers of fibrosis (TIMP-1 and PIIINP) and vasculopathy (MMP-9) were additionally elevated. ACE2 RNA expression during severe COVID-19 often responded within hours to convalescent plasma. Analogous to oncogenesis, we speculate that potent, persistent, cryptic processes following COVID-19 (the renin-angiotensin system (RAS), fibrosis and vasculopathy) initiate or promote post-COVID-19 conditions (PCC) in susceptible individuals. CONCLUSIONS: This work elucidates biological and temporal plausibility for ACE2, TIMP1, PIIINP and MMP-9 in the pathogenesis of PCC. Intersection of these independent systems is uncommon and may in part explain the rarity of PCC.

Bergenin inhibits growth of human cervical cancer cells by decreasing Galectin-3 and MMP-9 expression.

Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus. Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.

Hypoxia exosome derived CEACAM5 promotes tumor-associated macrophages M2 polarization to accelerate pancreatic neuroendocrine tumors metastasis via MMP9.

Exosomes play significant roles in the communications between tumor cells and tumor microenvironment. However, the specific mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic neuroendocrine tumors (pNETs) are not well understood. This study aims to investigate these mechanisms and made several important discoveries. We found that hypoxic exosomes derived from pNETs cells can activate tumor-associated macrophages (TAM) to the M2 phenotype, in turn, the M2-polarized TAM, facilitate the migration and invasion of pNETs cells. Further investigation revealed that CEACAM5, a protein highly expressed in hypoxic pNETs cells, is enriched in hypoxic pNETs cell-derived exosomes. Hypoxic exosomal CEACAM5 was observed to induce M2 polarization of TAM through activation of the MAPK signaling pathway. Coculturing pNETs cells with TAM or treated with hypoxic exosomes enhanced the metastatic capacity of pNETs cells. In conclusion, these findings suggest that pNETs cells generate CEACAM5-rich exosomes in a hypoxic microenvironment, which in turn polarize TAM promote malignant invasion of pNETs cells. Targeting exosomal CEACAM5 could potentially serve as a diagnostic and therapeutic strategy for pNETs.

Impact of Inflammatory Markers and Senescence-Associated Secretory Phenotype in the Gingival Crevicular Fluid on the Outcomes of Periodontal Regeneration.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1ß, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1ß and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.

Early Effects of Modern Radiotherapy for Lung Cancer on Endothelial Damage and Myocardial Fibrosis: A Prospective Single-Center Study.

Radiotherapy (RT) may have a cardiotoxic effect on the heart and cardiovascular system. Postulated mechanisms mediating these complications include vascular endothelium damage and myocardial fibrosis. The aim of our study was to assess endothelial damage and myocardial fibrosis in the early period after RT on the basis of cardiac biomarkers and in relation to the radiation dose applied to individual heart structures in patients treated for non-small-cell lung cancer. This single-center prospective study included consecutive patients with lung cancer (LC) who were referred for treatment with radiochemotherapy (study group) or chemotherapy (control group). The study protocol included performing an echocardiographic examination, a standard ECG examination, and collecting blood samples for laboratory tests before starting treatment for lung cancer in the first week after completing RT (after four cycles of chemotherapy in the control group) and after 12 weeks from the end of treatment. The study included 23 patients in the study group and 20 patients in the control group. Compared to the baseline values, there was a significant increase in total cholesterol concentration in the study group immediately after the end of RT, which persisted for three months after the end of therapy. After taking into account the use of statins in the analysis, it was found that an increase in total cholesterol concentration after oncological treatment was observed only among patients who did not use statins. Taking into account the assessment of myocardial fibrosis markers, there were no significant changes in the concentration of matrix metallopeptidase 9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in the study group. In patients treated with radiochemotherapy, there was a significant increase in the concentration of intercellular adhesion molecule 1 (ICAM-1) immediately after RT, when compared to the baseline. After taking into account the use of statins, an increase in ICAM-1 concentration immediately after RT was observed only in patients who did not use statins. There was also a significant correlation between the radiation dose received by the left anterior descending coronary artery (LAD) and left circumferential coronary artery, and vascular cell adhesion protein 1 (VCAM-1) concentration measured at three months after the end of RT. Immediately after completion of radiotherapy, a significant increase in the level of ICAM-1 is observed indicating endothelial damage. The radiation dose to coronary arteries should be minimized, as it correlates with the concentration of VCAM-1. The use of statins may prevent the increase in total cholesterol and ICAM-1 concentration after irradiation for lung cancer; however, further studies designed for this specific purpose are necessary to confirm the effectiveness of statins in this area.

Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

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.

Comparing two mucin secretagogues for the treatment of dry eye disease: a prospective randomized crossover trial.

This study aimed to compare the clinical efficacy and investigate patients' preferences for two mucin secretagogues in the treatment of dry eye disease (DED). Thirty patients with DED were randomly treated with either 3% diquafosol or 2% rebamipide ophthalmic solution for 4 weeks, followed by an additional 4-week treatment using the other eye drop after a 2-week washout period. Objective and subjective assessments, including the corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer 1 test, tear osmolarity, tear matrix metalloproteinase-9 (MMP-9), lipid layer thickness (LLT) and ocular surface disease index (OSDI), were performed at baseline, 4 weeks, 6 weeks, and 10 weeks. Patient preferences were assessed based on four categories (comfort, efficacy, convenience, willingness to continue) using a questionnaire and the overall subjective satisfaction score for each drug was obtained at the end of the trial. In total, 28 eyes from 28 patients were included in the analysis. Both diquafosol and rebamipide significantly improved the OSDI (p = 0.033 and 0.034, respectively), TBUT (p < 0.001 and 0.026, respectively), and corneal (p < 0.001 and 0.001, respectively) and conjunctival (p = 0.017 and 0.042, respectively) staining after 4 weeks of treatment. An increase in Schirmer test scores was observed only after rebamipide treatment (p = 0.007). No significant changes were detected in tear osmolarity, MMP-9, and LLT following both treatments. The patients' preference was slightly greater for diquafosol (46.4%) than rebamipide (36.7%), presumably due to rebamipide's bitter taste. The self-efficacy of both drugs and overall satisfaction scores were comparable. These findings indicate that two mucin secretagogues showed comparable effects in ameliorating symptoms and improving signs (TBUT, corneal and conjunctival staining) in patients with DED.

Inflammatory imbalance in tracheal aspirate of very preterm newborns is associated with airway obstruction and lung function deficiencies at school age: a cohort study.

OBJECTIVE: A low expression of club cell secretory protein (CC16) and high levels of proinflammatory cytokines at preterm birth are associated with airway inflammation and more severe neonatal lung disease. The present study aimed to investigate if low levels of CC16, proinflammatory cytokines and vascular endothelial growth factors (VEGF) in tracheal aspirate early after birth were associated with lung function impairment at school age. PATIENTS AND METHODS: Participants were 20 children, born very preterm (median gestational age 25+3 weeks+days, IQR: 24+1-27+0 weeks+days), who had tracheal aspirates collected during mechanical ventilation in their first day of life. CC16, cytokines, VEGF and matrix metalloproteinase-9 were measured in the tracheal aspirate and later correlated to results from advanced lung function measurements at 12 years of age. RESULTS: Low levels of CC16 and high levels of the proinflammatory cytokines IL-1ß and TNF-α in tracheal aspirate were associated with airway obstruction at school age but not with other lung function parameters. The correlation with airway obstruction was even stronger when the ratio between the respective proinflammatory cytokine and CC16 was used. In addition, low levels of VEGF and CC16 were associated with impaired diffusion capacity of the lung. CONCLUSIONS: An imbalance in inflammatory mediators and growth factors in the lungs at birth may have consequences for airway function and vasculature at school age in preterm born children.

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model.

One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

Glutamine Protects against Mouse Abdominal Aortic Aneurysm through Modulating VSMC Apoptosis and M1 Macrophage Activation.

Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.

Tuning Peptide-Based Nanofibers for Achieving Selective Doxorubicin Delivery in Triple-Negative Breast Cancer.

Introduction: The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options. Purpose: In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy. Methods: Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed. Results: The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox. Discussion: We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.

Cardioprotective effects of the aqueous extract of Echinops cephalotes on myocardial ischemia-reperfusion in rats by modulation of MMP-2, MMP-9, TIMP, and oxidative stress.

Echinops plants have received great attention for the treatment of many diseases due to pharmacological properties such as their antidiabetic, antioxidant, and anti-inflammatory characteristics. The major purpose of the present study was to investigate the cardioprotective benefits of Echinops cephalotes (Ech) against myocardial ischemia-reperfusion (MI/R) injury. Male Wistar rats were randomly allocated to three groups: sham, MI, and MI + Ech. The left coronary artery (LAD) was blocked for 30 minutes to induce MI. In the treatment group, rats were given 150 mg/kg/day of Ech extract for 28 days. Aqueous extracts were made from Echinops plants. To study heart function, fibrosis, cardiac damage indicators, and oxidative stress factors, echocardiography, Masson's trichrome staining, and biochemical tests were used. The expression of matrix metalloproteinase 2 and 9 (MMP2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) was determined using Western blotting. Tissue damage was assessed using hematoxylin and eosin staining. MI group exhibited significantly reduced ejection fraction (EF) and fractional shortening (FS), enhanced levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), cardiac Troponin I (cTnI), and malondialdehyde (MDA), as well as a decrease in the Glutathione (GSH) tissue content, reduced activity of superoxide dismutase (SOD), increasing fibrosis, upregulations of MMP-2 and MMP-9, and reduction of TIMP compared to the sham group. The findings suggest that Ech in particular, could be a promising therapeutic agent to reduce the damage in MI by targeting oxidative stress and modulating the activities of matrix metalloproteinases and their tissue inhibitors.

Immunohistochemical-properties of the dermal embryonic telocytes.

The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.

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.

Transplantation of Mesenchymal Stem Cells Derived from Old Rats Improves Healing and Biomechanical Properties of Vaginal Tissue Following Surgical Incision in Aged Rats.

Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women's lives. These include pelvic organ prolapse (POP), urinary incontinence, and sexual dysfunction. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Prolapse recurrence rates following surgery were reported to be as high as 30%. This may be attributed to ineffective healing in the elderly. Autologous stem cell transplantation during surgery may improve surgical results. In our previous studies, we showed that the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) from young donor rats improved the healing of full-thickness vaginal surgical incision in the vaginal wall of old rats, demonstrated by both histological and functional analysis. In order to translate these results into the clinical reality of autologous MSC transplantation in elderly women, we sought to study whether stem cells derived from old donor animals would provide the same effect. In this study, we demonstrate that MSC transplantation attenuated the inflammatory response, increased angiogenesis, and exhibited a time-dependent impact on MMP9 localization. Most importantly, transplantation improved the restoration of the biomechanical properties of the vagina, resulting in stronger healed vaginal tissue. These results may pave the way for further translational studies focusing on the potential clinical autologous adjuvant transplantation of MSCs for POP repair for the improvement of surgical outcomes.