Matrix Metalloproteinase-9 Levels Research Articles

MMP-8 causes leftward shift in end-diastolic pressure-volume relationship and may explain the development of diastolic dysfunction in septic cardiomyopathy.

Septic cardiomyopathy (SCM) with diastolic dysfunction carries a poor prognosis, and the mechanisms underlying the development of diastolic dysfunction remain unclear. Matrix metalloproteinase-8 (MMP-8) is released from neutrophils and degrades collagen I. MMP-8 levels correlate with SCM severity. We scrutinized, for the first time, the direct impact of MMP-8 on cardiac systolic and diastolic functions. Isolated rat hearts were perfused with Krebs-Henseleit solution in a Langendorff setup with computer-controlled filling pressures of both ventricles in an isovolumetric regime. The end-diastolic pressure (EDP) varied periodically between 3 and 20 mmHg. After baseline recordings, MMP-8 (100 µg/mL) was added to the perfusion. Short-axis views of both ventricles were continuously acquired by echocardiography. MMP-8 perfusion resulted in a progressive decline in peak systolic pressures (Psys) in both ventricles, but without significant changes in their end-systolic pressure-area relationships (ESPARs). Counterintuitively, conspicuous leftward shifts of the end-diastolic pressure-area relationships (EDPARs) were observed in both ventricles. The left ventricle (LV) end-diastolic area (EDA) decreased by 32.8 ± 5.7% (P = 0.008) at an EDP of 10.5 ± 0.4 mmHg, when LV Psys dropped by 20%. The decline of Psys was primarily due to the decrease in EDA, and restoring the baseline EDA by increasing EDP recovered 81.33 ± 5.87% of the pressure drop. Collagen I generates tensile (eccentric) stress, and its degradation by MMP-8 causes end-diastolic pressure-volume relationship (EDPVR) leftward shift, resulting in diastolic and systolic dysfunctions. The diastolic dysfunction explains the clinically observed fluid unresponsiveness, whereas the decrease in end-diastolic volume (EDV) diminishes the systolic functions. MMP-8 can explain the development of SCM with diastolic dysfunction.NEW & NOTEWORTHY MMP-8, released from activated neutrophils and macrophages, is markedly elevated in sepsis, correlating with sepsis severity and mortality. MMP-8 targets collagen I of the cardiac ECM and induces diastolic dysfunction with fluid unresponsiveness, associated with decreased EDV, reduced sarcomere length, and diminished systolic function. Unlike other MMPs that predominantly cleave collagen-III and contribute to cardiac dilatation, thereby increasing sarcomere length, MMP-8 leads to a leftward shift in the EDPVR, resulting in diastolic and systolic dysfunctions.

Levels of Matrix Metalloproteinase-9 (MMP-9) and its gene polymorphism of Hydatid Cyst Disease in an Infected Patients

Hydatid cystic disease is an economic burden in Iraq since it decreases the productivity of sheep, goats, cows, and camels by making the organs unpalpable for human consumption, hence weight-loss and ill health. This is one of the most common zoonosis diseases shared between human beings and animals and appears in man hosts inlcuded some organes, such as liver and lung as hydatid cyst . it causes many complications that may lead to death in repured parasites. Now there are no safe and effective in the fight against this parasite, and the search for such medications is in research. The Matrix Metalloproteinase-9 is a one of the enzymes that belong to the family of matrix metalloproteinases (MMPs), which play a crucial role in the proteolytic degradation of the extracellular matrix (ECM). These enzymes have a zinc ion in the active site that is important for their proteolytic activity. MMP-9, also known as Gelatinase B, catalyzes gelatin and degrades components of the ECM, including abundant type IV collagen in basement membranes. MMP-9 plays an important role in various biological processes, including tissue remodeling, angiogenesis, and tissue inflammation. The objective of the study is to determine the impact of MMP-9 serum levels and specific single nucleotide polymorphisms (SNPs) rs17576 and rs76070157 on patients with hydatid disease, in comparison to a control group of healthy individuals. A total of (62) patients diagnosed with hydatid disease, consisting of 18 males and 44 females, were compared to a control group of(75) individuals, comprising 29 males and 46 females .The study examined the MMP-9 rs17576 and rs76070157 )SNPs( in patients with hydatid disease, comparing them to a control group of healthy individuals. The study revealed no statistically significant difference in the average age between the two groups at a significance level of 0.05. Additionally, the study found higher concentrations of MMP-9 in the sera of the infected group (20.40 ± 1.52 pg/µl) compared to the control group (19.49 ± 1.62 pg/µl). The rs17576 )SNPs( data indicated that the TT genotype and T allele exhibited a slightly higher frequency percentage in the group of patients with hydatid disease compared to the healthy group, however this difference was not statistically significant. The values are (98.4% and 99.0%) the value of pc is 0.001. The elevated odds ratio (OR) associated with the TT genotype and T allele may serve as a potential risk factor for hydatid disease. The rs17576 SNPs displayed genotypes that were not in accordance with Hardy-Weinberg equilibrium. However, these genotypes were consistent with those observed in a control group. The GG genotype showed a significant increase in frequency compared to the control group (100.0% vs. 100.0%), while the G allele exhibited a non-significant increase in frequency. The odds ratio (OR) for the TG genotype was 3.68, and the p-value (pc) was 0.05.Elevated value could potentially increase the risk of hydatid disease. The presence of the TG genotype was shown to considerably increase the frequency percentage in the group of patients with hydatid disease. The odds ratio (OR) value of 1.6 suggests that it may be a risk factor for hydatid disease, with a frequency of 98.4% compared to 0.99 % in the control group. The p-value of 0.001 indicates a statistically significant association. The GG genotype was present in (0%) of the affected group but absent (100.0%) in the healthy group. The odds ratio (OR) of 3.68, with a p-value of 0.001, suggests that the GG genotype is associated with a significantly lower risk of hydatid disease.

Involvement of interferon γ-producing mast cells in immune responses against melanocytes in vitiligo requires MrgX2 activation.

Increasing evidence indicates that oxidative stress and interferon γ (IFNγ)-driven cellular immune responses are responsible for the pathogenesis of vitiligo. However, the connection between oxidative stress and the local production of IFNγ in early vitiligo remains unexplored. The aim of this study was to identify the mechanism underlying the production of IFNγ by mast cells and its impact on vitiligo pathogenesis. Skin specimens from the central, marginal, and perilesional skin areas of active vitiligo lesions were collected to characterize changes of mast cells, CD8+ T cells, and IFNγ-producing cells. Cell supernatants from hydrogen peroxide (H2O2)-treated keratinocytes (KCs) were harvested to measure levels of soluble stem cell factor (sSCF) and matrix metalloproteinase (MMP)-9. A murine vitiligo model was established using Mas-related G protein-coupled receptor-B2 (MrgB2, mouse ortholog of human MrgX2) conditional knockout (MrgB2-/-) mice to investigate IFNγ production and inflammatory cell infiltrations in tail skin following the challenge with tyrosinase-related protein (Tyrp)-2 180 peptide. Potential interactions between the Tyrp-2 180 peptide and MrgX2 were predicted using molecular docking. The siRNAs targeting MrgX2 and the calcineurin inhibitor FK506 were also used to examine the signaling pathways involved in mast cell activation. IFNγ-producing mast cells were closely aligned with the recruitment of CD8+ T cells in the early phase of vitiligo skin. sSCF released by KCs through stress-enhanced MMP9-dependent proteolytic cleavage recruited mast cells into sites of inflamed skin (Perilesion vs. lesion, 13.00 ± 4.00/HPF vs. 26.60 ± 5.72/HPF, P <0.05). Moreover, IFNγ-producing mast cells were also observed in mouse tail skin following challenge with Tyrp-2 180 (0 h vs. 48 h post-recall, 0.00 ± 0.00/HPF vs. 3.80 ± 1.92/HPF, P <0.05). The IFNγ+ mast cell and CD8+ T cell counts were lower in the skin of MrgB2-/-mice than in those of wild-type mice (WT vs. KO 48 h post-recall, 4.20 ± 0.84/HPF vs. 0.80 ± 0.84/HPF, P <0.05). Mast cells activated by MrgX2 serve as a local IFNγ producer that bridges between innate and adaptive immune responses against MCs in early vitiligo. Targeting MrgX2-mediated mast cell activation may represent a new strategy for treating vitiligo.

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer.

In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection. The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls. No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001). The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

HLTF/SERPINE1 Axis Plays a Crucial Pro-Oncogenic Role in the Progression from Cervical Precancerous Lesions to Cervical Carcinoma in vitro

Objectives: Cervical carcinoma (CC) is prevalent among women worldwide with increasing risk. Finding effective methods for treating CC is of utmost importance. The aim of this study was to investigate the effect of SERPINE1 on the progression of cervical precancerous lesions to CC. Design: This study used transcriptome sequencing and in vitro cell line. Participants/Materials: Cervical precancerous lesions and CC samples and human cervical epithelial immortalized cell line H8, human CC cell lines HeLa, and CaSki were involved in this study. Setting and Methods: Next-generation sequencing was applied to identify 100 differentially expressed genes from cervical precancerous lesions and CC samples. With the application of the Search Tool for the Retrieval of Interacting Genes (STRING) database, we carried out the protein-protein interaction network analysis, thus screening out serine protease inhibitor clade E member 1 (SERPINE1) with significant upregulation in CC cells. The helicase-like transcription factor (HLTF) was predicted as the upstream transcription factor using Human Transcription Factor Database (HumanTFDB). The chromatin immunoprecipitation (ChIP) experiment was conducted to validate the interaction between SERPINE1 and HLTF. The immunohistochemistry was employed to determine the expression of SERPINE1 and HLTF in CC tissues. Following the upregulation or downregulation of SERPINE1 and HLTF, the real-time quantitative reverse transcription polymerase chain reaction was carried out to assess mRNA expression levels of SERPINE1 and HLTF in cells. Cell viability, migration, and invasion were evaluated using MTT assay, cell scratch assay, and Transwell assay, respectively. Western blot analysis was conducted to assess changes in the expression levels of matrix metalloproteinases and proteins related to epithelial-mesenchymal transition (EMT). Results: The ChIP experiment confirmed the interaction between HLTF and SERPINE1. HLTF and SERPINE1 were upregulated in CC tissues and cells, and silencing SERPINE1 inhibited the EMT process and viability, migration, and invasion of CC cells. However, overexpression of SERPINE1 in CC cells showed the opposite trend. Rescue experiments demonstrated that silencing HLTF repressed CC cell viability, migration, and invasion, which could be restored by overexpressing SERPINE1. Limitations: The effect of the HLTF/SERPINE1 axis on CC malignant progression has not been confirmed by in vivo experiments. Conclusion: HLTF transcriptionally activates SERPINE1, promoting the progression from cervical precancerous lesions to CC.

New Insights into the Pathophysiology of Coronary Artery Aneurysms.

Coronary aneurysms are typically defined as sections of a coronary artery where the diameter is more than 1.5 times that of an adjacent normal segment. In rare circumstances, these aneurysms can become exceedingly large, leading to the classification of giant coronary artery aneurysms. Despite their occurrence, there is no clear consensus on the precise definition of giant coronary artery aneurysms, and their etiology remains somewhat ambiguous. Numerous potential causes have been suggested, with atherosclerosis being the most prevalent in adults, accounting for up to 50% of cases. In pediatric populations, Kawasaki disease and Takayasu arteritis are the primary causes. Although often discovered incidentally, coronary artery aneurysms can lead to severe complications. These complications include local thrombosis, distal embolization, rupture, and vasospasm, which can result in ischemia, heart failure, and arrhythmias. The optimal approach to medical, interventional, or surgical management of these aneurysms is still under debate and requires further clarification. This literature review aims to consolidate current knowledge regarding coronary artery aneurysms' pathophysiology, emphasizing their definition, causes, complications, and treatment strategies. Recent research has begun to explore the molecular mechanisms involved in the formation and progression of coronary artery aneurysms. Various molecules, such as matrix metalloproteinases (MMPs), inflammatory cytokines, and growth factors, play crucial roles in the degradation of the extracellular matrix and the remodeling of vascular walls. Elevated levels of MMPs, particularly MMP-9, have been associated with the weakening of the arterial wall, contributing to aneurysm development. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1β and IL-6) have been implicated in promoting inflammatory responses that further degrade vascular integrity. Additionally, growth factors such as vascular endothelial growth factor (VEGF) may influence angiogenesis and vascular remodeling processes. Understanding these molecular pathways is essential for developing targeted therapies aimed at preventing the progression of coronary artery aneurysms and improving patient outcomes.

Levels of matrix metalloproteinase-1 (MMP-1), MMP-2, MMP-3, osteopontin, pentraxin-3, and thymic stromal lymphopoietin in crevicular fluid samples from peri-implantitis, periodontitis, and healthy sites.

Periodontitis and peri-implantitis are chronic inflammatory diseases characterized by the destruction of supporting tissues. Despite some similarities, it is essential to understand the differences in how these diseases elicit unique host responses within the oral tissues, including the production of selected matrix metalloproteinases (MMPs) and inflammatory mediators involved in tissue remodelling. The aim of this study was to evaluate the levels of proteolytic enzymes MMP-1, MMP-2, MMP-3, as well as the inflammatory mediators osteopontin (OPN), pentraxin-3 (PTX3), and thymic stromal lymphopoietin (TSLP) in crevicular fluid samples collected from healthy, periodontitis-affected, and peri-implantitis sites. Gingival crevicular fluid (GCF) and peri-implant crevicular fluid (PICF) samples were collected from healthy and diseased teeth and implant sites of 163 patients. The MMP-1, MMP-2, MMP-3, OPN, PTX3, and TSLP levels were determined using commercially available immunoassays. A linear mixed model procedure was adopted for multilevel analyses, using biomarker levels as the outcome variable to compare two types of sites. The diagnostic accuracy of the biomarkers was evaluated by Youden's index to estimate the sensitivity, specificity and the area under curve (AUC). The levels of MMP-1, MMP-2, MMP-3, OPN, and TSLP were higher at sites with periodontitis and peri-implantitis compared to the levels at sites with healthy teeth and healthy implants. No significant differences were observed in the levels of the measured markers between the sites diagnosed with periodontitis and those diagnosed with peri-implantitis. The highest diagnostic potential at implant sites was found for MMP-2 (AUC = 0.74) and TSLP (AUC = 0.72). The highest AUC (0.82) at tooth sites was found for OPN. The findings indicate that the proteolytic enzyme MMP-2 and the cytokine TSLP might be potential biomarkers for both periodontitis and peri-implantitis, whereas the proinflammatory cytokine OPN may serve as a biomarker for periodontitis. Further studies are required to confirm the utility of these biomarkers and explore their potential clinical applications.

Anti-inflammatory activity of the combination Ardisia humilis Vahl. and Curcuma xanthorrhiza Roxb. extract on an osteoarthritis rat model

This study aimed to evaluate the anti-inflammatory activity of the combination of Ardisia humilis Vahl. and Curcuma xanthorrhiza Roxb. (AC) extract in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) rat model. AC was administered orally to OA rats (240, 480, and 960 mg/kg bw) for three weeks. The control and model groups comprised OA rats treated with diclofenac sodium and carrier, respectively. AC-treated rats exhibited a significant reduction in oedema volume compared to those of the model group (p < 0.05). Notably, AC, at 960 mg/kg bw, significantly decreased inflammatory cytokines TNF-α and IL-1β, along with matrix metalloproteinase-9 (MMP-9) levels compared to those of the model group (p < 0.05). AC's attenuation of OA progression was also observed through haematoxylin and eosin (H&E) and Safranin O-fast green analysis. A phytochemical study showed AC contained phenolic, flavonoid, curcumin, demethoxycurcumin, and bisdemethoxycurcumin compounds. This study concludes that AC alleviated OA progression through anti-inflammatory effects and depressed MMP-9 levels.

Effect of Human Platelet-Rich Fibrin Lysate on Collagen Type I, Collagen Type III, and Matrix Metalloproteinase 1 : A Protocol Study on Rat Models with Pelvic Organ Prolapse

Background Pelvic organ prolapse (POP) is a prevalent condition caused by weakened pelvic floor support structures. Extracellular matrix alterations, including changes in collagen type I, collagen type III, and matrix metalloproteinase 1 (MMP-1), contribute to the pathogenesis of this condition. Human platelet-rich fibrin lysate (hPRF-L) is a novel regenerative treatment that has shown beneficial results in treating structural weaknesses related to various pelvic floor diseases, including POP. Methods This study protocol aims to investigate the effects of hPRF-L injection on collagen I, III, and MMP-1 in the vaginal mucosa of a rat POP model. POP will be induced in female Sprague-Dawley rats, which will be randomly assigned to control, sham, and hPRF-L treatment groups. The hPRF-L group will receive weekly injections of hPRF-L (25, 50, or 75 μL) into the vaginal mucosa for 4 weeks. Vaginal tissue samples will be collected, and collagen type I, collagen type III, and MMP-1 expression will be evaluated using quantitative reverse transcription polymerase chain reaction and immunohistochemical analyses. Data analysis will be performed with ANOVA and post-hoc tests. Discussion The findings from this study protocol are expected to provide valuable insights into the mechanisms by which hPRF-L impacts the structural integrity of the pelvic floor. By elucidating these mechanisms, this study aims to inform future POP treatment strategies. The anticipated results are an increase in collagen type I and III expression and a reduction in MMP-1 levels in the hPRF-L treatment group compared to the control and sham groups. These outcomes could support the use of hPRF-L as a regenerative therapy for managing POP, offering a potential alternative to more invasive surgical interventions. Conclusion The expected results will contribute to the development of less invasive treatments for POP, improving patient outcomes and quality of life.

Comparative Study Between the Effects of High Doses of Rosuvastatin and Atorvastatin on Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

Most studies reported that treating ST-Elevation Myocardial Infarction (STEMI) patients with high doses of rosuvastatin or atorvastatin could improve left ventricular remodeling and cardiac function. The current study compared the impact of high doses of rosuvastatin and atorvastatin on hypertrophy, fibrosis markers, serum inflammatory markers, and left ventricular function in STEMI patients after primary percutaneous coronary intervention (PCI). After primary PCI, eighty STEMI patients were randomized to receive either 20 mg of rosuvastatin (n = 40) or 40 mg of atorvastatin (n = 40) once daily for 3 months. Soluble Suppression of Tumorigenicity-2 (sST2), Matrix Metalloproteinase-9 (MMP9), C-Reactive Protein (CRP), lipid parameters, liver enzymes, and echocardiographic parameters were assessed for the two groups at baseline and after 3 months. After 3 months of treatment, a statistically significant reduction was observed in the rosuvastatin group regarding the levels of CRP (16 ± 6 vs. 20 ± 10 mg/L, P = 0.024) and MMP9 (104 ± 33 vs. 130 ± 42 ng/L, P = 0.003) compared with the atorvastatin group. The median percentage decrease in sST2 level in the rosuvastatin group was higher (6.1%) than in the atorvastatin group (2.3%) after 3 months of treatment. Also, in the rosuvastatin group, LVEF was significantly increased (48.5 ± 9 vs. 43.5 ± 11%, P = 0.029), while LVEDV and LVESV were significantly decreased compared to those of the atorvastatin group (101 [81/135] vs. 134 [100/150] ml, P = 0.041) (53 [37/75] vs. 73 [52/92] ml, P = 0.033), respectively. High-intensity rosuvastatin was superior to high-intensity atorvastatin in reducing the inflammatory response and myocardial fibrosis, thus improving ventricular remodeling and cardiac function better in STEMI patients. This randomized controlled trial was registered on October 11, 2022, on ClinicalTrials.gov under registration number: NCT05895123 "retrospectively registered".

Analysis of risk indicators for implant failure in patients with chronic periodontitis

Dental implant restoration shows an effective method for the rehabilitation of missing teeth. The failure rate of periodontal implants in patients with chronic periodontitis is associated with periodontal flora, inflammation, and long-term periodontal bone resorption caused by chronic periodontitis. However, the therapeutic effects of dental implant restoration on inflammation in patients with chronic periodontitis have not addressed. The purpose of this study is to evaluate the risk indicators for inflammation, bone loss and implant failure in patients with chronic periodontitis. A total of 284 patients with dental implant restoration were recruited and divided into periodontally healthy patients (n = 128) and chronic periodontitis patients (n = 156). Periodontal indices including probing depth (PD), sulcus bleeding index (SBI), plaque index (PLI), gingival bleeding (GIL) and bleeding on probing (BOP) were compared in two groups. Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels at baseline, 6 and 12 months after surgery, and the implant survival rate at 12 months after surgery, as well as the risk factors associated with failure of dental implant were also assessed. Outcomes demonstrated that patients in the chronic periodontitis group had higher values of periodontal indices than those in the periodontally healthy group. All inflammatory parameters in the chronic periodontitis group were higher than those in the periodontally healthy group and negatively associated with the chronic periodontal index (CPI) in chronic periodontitis patients. Chronic periodontitis patients had higher the prevalence of mucositis and peri-implantitis than patients with healthy periodontium. Implant diameter, length and design was associated with the risk of implant failure for chronic periodontitis patients receiving dental implant. The cumulative implant failure rate and incidence of implant fractures for chronic periodontitis patients at 12 months after surgery were 12.10% and 7.23% (p < 0.05), respectively, while were lower in the heathy periodontitis patients. Location, diameter, implant design, immediate loading and bone defect were risk indicators for bone loss for dental implant patients. The risk factors associated with failure of dental implant was higher in chronic periodontitis patients than patients in the periodontally healthy group (14.25% vs. 4.92%, p < 0.05). In conclusion, data in the current study indicate that inflammation is a risk indicator bone loss, implant fracture and implant failure in patients with chronic periodontitis.

Cellular responses following ex vivo lung exposure to the nerve agent VX – Potential for additional treatment targets?

Following inhalation exposure to organophosphorus nerve agents, symptoms rapidly develop and severe respiratory symptoms, such as bronchorrhea and bronchoconstriction are the leading causes of lethality. Nerve agent-induced lung injury is little investigated and the standard treatment for symptomatic relief targets the enzyme acetylcholinesterase and muscarinic acetylcholine and GABAergic receptors. In the present study, cellular responses in lung tissue during the acute (40 min) and extended phase (24 h) following severe exposure to the nerve agent VX have been investigated using an ex vivo rat precision-cut lung slice model including electrostimulation to induce a cholinergic response. Changes in protein amount, cell viability, together with, inflammatory and oxidative stress markers have been determined in both the lung tissue and incubation medium.During the acute phase, VX caused significantly increased airway contraction and decreased airway relaxation. Five micromolar of VX did not affect the sample protein levels and cell viability in lung tissue. Among seven markers of cellular responses investigated in the lung tissue, increased levels of heme oxygenase-1 and matrix metalloproteinase-9 together with decreased levels of glutathione in the incubation medium were observed in the acute phase following VX-exposure compared to electrostimulation only. No difference in cellular response was observed following VX-exposure for 24 h compared to the air control. In comparison, LPS-exposure resulted in time-dependent changes in all markers of inflammation and oxidative response.In conclusion, the present study demonstrated VX-specific patterns of oxidative responses in the lung, as well as, signs of inflammatory response and remodelling of extracellular matrix. These potential mechanisms of tissue injury should be further investigated for their potential as additional therapeutic targets during the acute phase of intoxication.

Effects of Vitamin C on the Gonad Growth, Texture Traits, Collagen Content and Synthesis Related Gene Expression of Sea Urchin (Mesocentrotus nudus).

The market value of sea urchin gonads is determined by the specific characteristics associated with gonad size and texture. Formulated feeds can effectively promote the gonad growth of sea urchins but cannot assure essential gonad texture traits. The objective of this study was to investigate the impact of vitamin C (VC) on the gonad growth, texture, collagen content, and the expression of genes involved in the collagen synthesis of sea urchins (Mesocentrotus nudus). Graded amounts of VC (0, 3000 and 6000 mg/kg) were supplemented to make three formulated feeds. Fresh kelp (Saccharina japonica) was used as the control diet. Each diet was randomly distributed to three tanks of M. nudus. The results indicated that the gonadosomatic index (GSI) and texture traits of M. nudus fed C3000 were significantly greater than those fed C0 and C6000. Collagen type I (Col I) in the gonads of M. nudus fed C3000 showed significantly greater areas than those fed C0 and C6000. Consistently, the expression levels of collagen alpha-1 (colp1α) of M. nudus fed C3000 were significantly higher than those fed C0 and C6000. As for the transforming growth factor beta (tgf-β)/Smads pathway, the expression levels of collagen synthesis genes (tgf-β receptor 1 and 2, smad nuclear-interacting protein 1 (snip1) and prolyl 4-hydroxylase subunit beta (p4hβ)) in the C3000 group were significantly greater than those in the C0, C6000 and kelp groups. On the contrary, the expression levels of collagen degradation genes (lysyl oxidase-like 2 (loxl2) and matrix metalloproteinase 14 (mmp14)) in the C3000 group were significantly lower than those in the C0, C6000 and kelp groups. In conclusion, VC at an addition level of 3000 mg/kg significantly increased the gonad texture and collagen contents of M. nudus, which could be accomplished by increasing collagen synthesis and inhibiting collagen degradation through the tgf-β/Smads pathway. These results could contribute to better understanding the beneficial effects of VC addition on the gonad texture quality of M. nudus.

Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is an inflammatory disorder where neutrophils play a key role. Excessive neutrophil activation leads to local hypoxia and tissue damage. Most research on neutrophil function has been conducted under atmospheric conditions (21% O2), which may not represent physiological or pathological conditions. This study aimed to determine the effects of hypoxia on neutrophil degranulation and cytokine production in AATD patients. Neutrophils isolated from 54 AATD patients (31 MZ; 8 SZ; 15 ZZ) and 7 controls (MM) were exposed to hypoxia (1% O2) for 4 h. Neutrophil degranulation was assessed by measuring elastase (NE), myeloperoxidase (MPO), lactoferrin, and matrix metalloproteinase-9 (MMP-9) levels using immunoassay-based methods. Pro-inflammatory (IL-8, IL-1 beta, IL-6, and TNF-alpha) and anti-inflammatory (IL-4 and IL-10) cytokine levels were assessed by a Luminex-based method. Our results indicate a significantly increased release of NE (p = 0.015), MPO (p = 0.042), lactoferrin (p = 0.015), and MMP-9 (p = 0.001) compared to controls. Pro-inflammatory cytokines show a significant rise in IL-8 (p = 0.019), a trend towards increased IL-1 beta (p = 0.3196), no change in IL-6 (p = 0.7329), and reduced TNF-alpha (p = 0.006). Anti-inflammatory cytokines show increased IL-4 (p = 0.057) and decreased IL-10 (p = 0.05703). Increased neutrophil degranulation and inflammatory phenotype are observed in AATD neutrophils under physiological hypoxia.

Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice.

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It is well known that maternal diet during pregnancy and lactation is vital for the early neurodevelopment of offspring. One-carbon (1C) metabolism, including folic acid and choline, plays a vital role in closure of the neural tube in utero. However, the impact of maternal dietary deficiencies in 1C on offspring neurological function following ischemic stroke later in life remains undefined. The aim of this study was to investigate inflammation in the blood and brain tissue of offspring from mothers deficient in dietary folic acid or choline. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. When offspring were 3 months of age, ischemic stroke was induced. One and a half months later, blood and brain tissue were collected. We measured levels of matrix metalloproteases (MMP)-2 and 9 in both plasma and brain tissue, and reported reduced levels of MMP-2 in ChDD male offspring in both tissue types. No changes were observed in MMP-9. This observation supports our working hypothesis that maternal dietary deficiencies in folic acid or choline during early neurodevelopment impact the levels of inflammation in offspring after ischemic stroke.

Unveiling molecular clues: Exploring IFNγ, IL-10, and MMP7 blood levels in gastric carcinoma patients

Objective: Gastric carcinoma is a leading cause of morbidity and mortality worldwide. Early detection can help reduce mortality rates. Biomarkers are being investigated globally for their potential in disease screening, monitoring, and follow-up in various cancers. However, currently, there is insufficient data on the role of biomarkers in gastric carcinoma. Material and Methods: This single center case control study was conducted from June 2018 to March 2021 from South India. Blood samples were collected from 85 patients diagnosed with gastric carcinoma and 85 apparently healthy individuals serving as the control group. The samples were collected in a fasting state. The serum levels of biomarkers interferon gamma (IFNγ), interleukin 10 (IL-10), and matrix metalloproteinase 7 (MMP7) were measured using enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Additionally, the levels of biomarkers were compared within the gastric cancer group based on disease location, stage, and histotype. Results: The serum levels of IFNγ and IL-10 were found to be significantly elevated in gastric carcinoma patients compared to the healthy control group. Both biomarkers exhibited high sensitivity and specificity in detecting carcinoma of the stomach. However, there was no significant difference in the serum level of MMP7 between gastric cancer patients and control group. Conclusion: IFNγ and IL-10 show promise as potential molecular biomarkers for the detection of gastric carcinoma. Further, well designed studies, involving larger and more diverse populations matched for stage and histological types, are necessary to establish the screening and monitoring utility of these biomarkers in gastric carcinoma.

Electrochemical detection of MMP-2 with enhanced sensitivity: Utilizing T7 RNA polymerase and CRISPR-Cas12a for neuronal studies

This study introduces a novel electrochemical biosensor for detecting Matrix Metalloproteinase-2 (MMP-2), a key biomarker in cancer diagnostics and tissue remodeling. The biosensor is based on a dual-amplification strategy utilizing T7 RNA polymerase isothermal amplification and CRISPR-Cas12a technology. The principle involves the release of a DNA template in the presence of MMP-2, leading to RNA synthesis by T7 RNA polymerase. This RNA activates CRISPR-Cas12a, which cleaves a DNA probe on the electrode surface, resulting in a measurable electrochemical signal.The biosensor demonstrated exceptional sensitivity, with a detection limit of 2.62 fM for MMP-2. This high sensitivity was achieved through the combination of transcriptional amplification and the collateral cleavage activity of CRISPR-Cas12a, which amplifies the signal. The sensor was able to detect MMP-2 across a wide dynamic range from 2 fM to 1 nM, showing a strong linear correlation between MMP-2 concentration and the electrochemical signal. In practical applications, the biosensor accurately detected elevated levels of MMP-2 in cell culture supernatants from HepG2 liver cancer cells, distinguishing them from normal LO2 liver cells. The use of an MMP-2 inhibitor confirmed the specificity of the detection. These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.

Arsenic Induced Oxidative Neural-Damages in Rat are Mitigated by Tea-Leave Extract via MMPs and AChE Inactivation, Shown by Molecular Docking and in Vitro Studies with Pure Theaflavin and AChE.

Chronic arsenic-exposure causes neuromuscular disorders and other health anomalies. Damage to DNA and cytoskeletal/extracellular matrix is brought on by reactive-oxygen-species (ROS)-induced intrinsic antioxidant depletion (thiols/urate). Therapeutic chelating-agents have multiple side-effects. The protection of (Camellia sinensis) tea-extract and role of uric-acid (UA) or allopurinol (urate-depletor) on arsenic-toxicity were verified in rat model. Camellia sinensis (CS dry-leaves), UA or allopurinol was supplemented to arsenic-intoxicated rats for 4-weeks. Purified theaflavins and their galloyl-ester were tested in-vitro on pure AChE (acetylcholinesterase) and their PDB/PubChem 3-D structures were utilized for in-silico binding studies. The primary chemical components were evaluated from CS-extracts. Biochemical analysis, PAGE-zymogram, DNA-stability comet analysis, HE-staining was performed in arsenic-exposed rat brain tissues. Animals exposed to arsenic showed symptoms of erratic locomotion, decreased intrinsic antioxidants (catalase/SOD1/uric acid), increased AChE, and malondialdehyde. Cerebellar and cerebrum tissue damages were shown with increased levels of matrix-metalloprotease (MMP2/9) and DNA damage (comets). Allopurinol- supplemented group demonstrated somewhat similar biochemical responses. In the CS-group brain tissues especially cerebellum is considerably protected which is evident from endogenous antioxidant and DNA and cytoskeleton protection with concomitant inactivation of MMPs and AChE. Present study indicates theaflavin-digallate (TFDG) demonstrated the highest inhibition of purified AChE (IC50 = 2.19 µg/ml with the lowest binding free-energy; -369.87 kcal/mol) followed by TFMG (IC50 = 3.86 µg/ml, -347.06 kcal/mol) suggesting their possible restoring effects of cholinergic response. Favorable responses in UA-group and adverse outcome in allo-group justify the neuro-protective effects of UA as an endogenous antioxidant. Role of flavon-gallate in neuro protection mechanism may be further studied.

The Effect of Salmon Calcitonin Adjuvant Treatment for Lumbar Spine Fracture: A Prospective, Randomized, Controlled Trial.

The study aimed at analyzing the therapeutic effect of salmon calcitonin on patients with lumbar spine fracture after operation. Eighty-eight cases with lumbar spine fracture who underwent percutaneous vertebroplasty (PVP) in The Huichang People's Hospital from February 2020 to February 2023 were separated into two groups. The 44 cases in the control group were treated with calcium carbonate and Vitamin D3 tablets, on the basis, the salmon calcitonin was applied to treat the 44 cases in study group. The pain degree, bone metabolism index and matrix metalloproteinase levels were determined and compared between two groups. Lumbar function and daily living activity ability in two groups were evaluated, and adverse reactions during treatment were observed. The pain degree in study group was alleviated after treatment for 3 mo compared with the control group (p<0.05). The bone specific alkaline phosphatase (BALP) and osteocalcin (OC) levels were increased, while beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) levels were decreased in study group after treatment for 3 mo compared with control group (p<0.05). After treatment for 3 mo, the serum matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) levels in study group were lower than those in control group (p<0.05). Three months after treatment, the Oswestry Disability Index (ODI) score was lower and Barthel Index (BI) score was higher in study group than those of control group (p<0.05). No severe adverse reactions were observed in both groups during treatment (p>0.05). Salmon calcitonin can relieve the pain degree, improve the levels of bone metabolism and matrix metalloproteinase, and improve the lumbar spine function and ability of daily living activity in patients with lumbar spine fracture.

Apolipoprotein E deficiency exacerbates blood-brain barrier disruption and hyperglycemia-associated hemorrhagic transformation after ischemic stroke

BackgroundThe polymorphism of the apolipoprotein E (ApoE) gene has been implicated in both the susceptibility to neurodegenerative disease and the prognosis of traumatic brain injury (TBI). However, the influence of ApoE on the risk of hemorrhagic transformation (HT) after acute ischemic stroke remains inconclusive. The present study aimed to investigate the potential impact of ApoE deficiency on the risk of hyperglycemia-associated HT and to elucidate the underlying mechanisms. MethodsWild-type (WT) and ApoE knockout (ApoE−/−) mice were injected with 50 % glucose to induce hyperglycemia and subsequently subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO). The mortality, neurological function, HT incidence and HT grading-score were evaluated at 24 hours after reperfusion. To evaluate the integrity of blood-brain barrier (BBB), the immunoglobulin G (IgG) leakage and the protein expressions of tight junctions (TJs) were detected using immunofluorescent staining and western blotting. Finally, the levels of matrix metalloproteinases (MMP)-2/9, microglial activation and proinflammatory mediators were investigated using immunofluorescent staining and western blotting. ResultsApoE−/− mice exhibited increased mortality and exacerbated neurological impairment, concomitant with more severe hyperglycemia-associated HT 24 hours post-reperfusion. Meanwhile, ApoE deficiency exacerbated the disruption of BBB, characterized by increased leakage of IgG, aggravated degradation of TJs and microvascular basement membranes. Furthermore, ApoE deficiency further aggravated the upregulation of MMP-2/9 and microglia-triggered neuroinflammation. ConclusionsOur findings demonstrate that the absence of ApoE exacerbates neurological impairment and hyperglycemia-associated HT in ischemic stroke mice, which is closely associated with MMP-2/9 signaling and neuroinflammation-mediated disruption of BBB.