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BACKGROUND: Intervertebral disc degeneration is caused by damage and degeneration of the nucleus pulposus and annulus fibrosus tissues inside the intervertebral disc, resulting in structural and functional changes of the intervertebral disc. However, there is yet no effective drug treatment for intervertebral disc degeneration. OBJECTIVE: To investigate the inhibitory effect of syringin on intervertebral disc degeneration. METHODS: A total of 10 male Sprague-Dawley rats were selected, and the coccygeal intervertebral disc (Co4/Co5) of each rat was set as model group, Co5/Co6intervertebral disc as syringin group, and Co6/Co7 intervertebral disc as control group. The control group did not receive any treatment. In the model group and syringin group, a miniature puncture needle was used to puncture the annulus fibrosus to establish an intervertebral disc degeneration model. Immediately after modeling, 2. 5μL of normal saline and syringin solution (5μmol/L) were given in the model and syringin groups, respectively. Four weeks after injection, the samples were taken. The degree of intervertebral disc degeneration in rats was observed by hematoxylin-eosin and safranine O-fast green staining. The expressions of type II collagen, aggrecan and matrix metalloproteinases 3 and 13 in intervertebral disc tissue were analyzed by immunohistochemical staining. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that in the model group, the height of intervertebral disc decreased, the cartilage endplate became thinner and cracked, the fibrous ring structure was disordered and cracked, and the nucleus pulposus disappeared;in the syringin group, the height of intervertebral disc was normal or slightly lower than that in the control group, the degree of cartilage endplate degeneration was lighter than that in the model group, the fiber circle permutation was relatively regular with no cracks, and the nucleus pulposus was partially shrunk. Safranine O-fast green staining showed that in the model group, the cartilage endplate of the intervertebral disc was defective and the calcified layer of cartilage became thinner, showing obvious degeneration. The structure and morphology of intervertebral disc cartilage endplate in the syringin group recovered to some extent. Immunohistochemical staining showed that, compared with the control group, the expressions of type II collagen and aggrecan in the intervertebral disc cartilage were decreased in the model group (P＜0. 000 1), while the expressions of matrix metalloproteinases 3 and 13 increased (P＜0. 000 1). Compared with the model group, the expressions of type II collagen and aggrecan in the intervertebral disc cartilage tissue were increased in the syringin group (P＜0. 001, P＜0. 000 1), while the expressions of matrix metalloproteinases 3 and 13 decreased (P＜0. 001, P＜0. 000 1). These results showed that syringin could improve the structure and function of intervertebral disc by inhibiting the expression of matrix metalloproteinases 3 and 13 and increasing the expression of type II collagen and aggrecan, thus preventing and slowing down the procession of intervertebral disc degeneration [ABSTRACT FROM AUTHOR]

The inflammation caused by asthma exacerbation can lead to permanent changes in the airways and loss of lung function. Integrins are membrane receptors that interact with components of the extracellular matrix and cell adhesion molecules. It is known that these receptors can be found in soluble form in some conditions such as asthma, but it is unknown if exacerbation during asthma leads to soluble integrins. Our results indicated that asthma patients showed higher levels of soluble α1, α2, and β2 integrin subunits in their serum compared to controls, as confirmed by both ELISA and western blot. During asthma exacerbation, the levels of α2 and β2 integrin subunits increased even more compared to non‐exacerbation and controls, while the α1 integrin subunit decreased. Western blot analysis identified two β2 integrin subunits, one at 75 kDa and another at 120 kDa; the 120 kDa subunit increased during asthma exacerbation. The activity of matrix metalloproteinase 9 (MMP9) increased during exacerbation, while MMP2 remained unchanged. Lower forced expiratory volume in 1 second (FEV1) values were associated with higher expression levels of α2, β1, and β2 integrin subunits. Active and latent MMP9 were correlated with the levels of the β2 integrin subunit, which means that at low levels of active and latent MMP9, there are lower levels of β2 integrin subunit. In conclusion, asthma exacerbation leads to the presence of soluble integrins, particularly the β2 subunit, most likely due to MMP9‐induced proteolytic cleavage. [ABSTRACT FROM AUTHOR]

This study compared the effectiveness of various cleaning approaches, including spray rinsing, repreparing with diamond burs, and using phosphoric acid or sodium hypochlorite alone or with polyphenols (resveratrol or myricetin), in removing blood contamination from the dentine after adhesive light-curing. The contact angles of the treated surfaces were measured and scanning electron microscopy/ energy dispersive X-ray spectroscopy observation was performed. The bond strength and nanoleakage were assessed, and in situ zymography was performed before and after aging. Interactions between matrix metalloproteinase (MMP)−9 and polyphenols were evaluated using molecular dynamics and rhMMP-9 inhibition analyses. The destruction of sodium hypochlorite on collagen and the resistance of polyphenols-treated dentine collagen to enzymolysis were evaluated using the hydroxyproline (HYP) assay. The effect of polyphenols on dentine collagen crosslinking was assessed by Fourier Transform Infrared Spectroscopy. The repreparation group had the lowest contact angle compared to the other groups. The spray rinsing group had the lowest bond strength and highest amounts of nanoleakage. Cleaning with phosphoric acid or sodium hypochlorite alone removed the blood contaminants and parts of the adhesive; moreover, applying polyphenols further improved the bond strength and decreased nanoleakage and MMP activity after aging. Both polyphenols inhibited rhMMP-9 activity and promoted collagen crosslinking. Sodium hypochlorite showed the maximum HYP release when used alone, which was decreased after adding polyphenols. Phosphoric acid or sodium hypochlorite cleaning can remove blood contamination from the dentine surface after adhesive curing, and the addition of polyphenols can improve the durability of dentine bonding. [Display omitted] • Phosphoric acid or sodium hypochlorite cleaning removed blood and part of the cured adhesive. • Phosphoric acid or sodium hypochlorite cleaning restored dentine bonding influenced by blood contamination. • Resveratrol and myricetin improved the resistance of collagen to exogenous enzymes. • Resveratrol and myricetin inhibited MMP activity and promoted collagen cross-linking. • Resveratrol and myricetin can contribute to the durability of the dentine bonding. [ABSTRACT FROM AUTHOR]

Introduction: Achieving strong bond strength of adhesive systems to deep dentin is challenging. Various methods to improve bond strength to deep dentin have been investigated. Chlorhexidine (CHX) enhances the longevity of the bond between adhesives and dentin by inhibiting the collagenolytic activity of Matrix Metalloproteinases (MMPs). Benincasa hispida is a natural plant-based functional food containing minerals and vitamins that help prevent osteoporosis and improve bone health. Aim: To evaluate the Microshear Bond Strength (MSBS) of a 10-methacryloyloxydecyl-dihydrogen Phosphate-based (10-MDP) universal adhesive system to coronal dentin with different dentin surface pretreatments, specifically CHX and Benincasa hispida. Materials and Methods: An in-vitro pilot study was conducted at the Department of Conservative Dentistry and Endodontics, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India, from May 2023 to November 2023. Dentin discs (42) were prepared from human mandibular first molars. A standard etch-and-rinse protocol was performed on the discs. The specimens were assigned to different dentin pretreatments: Group-I (no pretreatment), Group-II (CHX) and Group-III (Benincasa hispida). CHX and Benincasa hispida were applied using micro applicator tips. A dentin bonding agent containing 10-MDP (DBA) was applied, photopolymerised and a composite restoration was fabricated. The MSBS to dentin was evaluated using a universal testing machine. The failure patterns were analysed using a stereomicroscope at 10x magnification. One-way Analysis of Variance (ANOVA) and Tukey's Honestly Significant Difference (HSD) HSD tests were used for statistical analysis, with a significance level set at α=0.05. Results: The mean MSBS values were 24.2732±5.41329 MPa for Group-III, 14.3848±4.23492 MPa for Group-II and 6.9724±3.15837 MPa for Group-I. Pretreatment of dentin with B. hispida resulted in significantly higher MSBS values compared to the other two groups (p<0.001*). Conclusion: Pretreatment with B. hispida significantly improved MSBS. Thus, B. hispida pretreatment may be beneficial in increasing dentin bond strength. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide (GLP)-1 receptor (GLP1R) agonists exert a multitude of beneficial cardiovascular effects beyond control of blood glucose levels and obesity reduction. They also have anti-inflammatory actions through both central and peripheral mechanisms. GLP1R is a G protein-coupled receptor (GPCR), coupling to adenylyl cyclase (AC)-stimulatory Gs proteins to raise cyclic 3'-5'-adenosine monophosphate (cAMP) levels in cells. cAMP exerts various anti-apoptotic and anti-inflammatory effects via its effectors protein kinase A (PKA) and Exchange protein directly activated by cAMP (Epac). However, the precise role and importance of cAMP in mediating GLP1R's anti-inflammatory actions, at least in the heart, remains to be determined. To this end, we tested the effects of the GLP1R agonist liraglutide on lipopolysaccharide (LPS)-induced acute inflammatory injury in H9c2 cardiac cells, either in the absence of cAMP production (AC inhibition) or upon enhancement of cAMP levels via phosphodiesterase (PDE)-4 inhibition with roflumilast. Methods & Results: Liraglutide dose-dependently inhibited LPS-induced apoptosis and increased cAMP levels in H9c2 cells, with roflumilast but also PDE8 inhibition further enhancing cAMP production by liraglutide. GLP1R-stimulated cAMP markedly suppressed the LPS-dependent induction of pro-inflammatory tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 cytokine expression, of inducible nitric oxide synthase (iNOS) expression and nuclear factor (NF)-kB activity, of matrix metalloproteinases (MMP)-2 and MMP-9 levels and activities, and of myocardial injury markers in H9c2 cardiac cells. The effects of liraglutide were mediated by the GLP1R since they were abolished by the GLP1R antagonist exendin(9–39). Importantly, AC inhibition completely abrogated liraglutide's suppression of LPS-dependent inflammatory injury, whereas roflumilast significantly enhanced the protective effects of liraglutide against LPS-induced inflammation. Finally, PKA inhibition or Epac1/2 inhibition alone only partially blocked liraglutide's suppression of LPS-induced inflammation in H9c2 cardiac cells, but, together, PKA and Epac1/2 inhibition fully prevented liraglutide from reducing LPS-dependent inflammation. Conclusions: cAMP, via activation of both PKA and Epac, is essential for GLP1R's anti-inflammatory signaling in cardiac cells and that cAMP levels crucially regulate the anti-inflammatory efficacy of GLP1R agonists in the heart. Strategies that elevate cardiac cAMP levels, such as PDE4 inhibition, may potentiate the cardiovascular, including anti-inflammatory, benefits of GLP1R agonist drugs. [ABSTRACT FROM AUTHOR]

The endothelial glycocalyx (eGC) is a carbohydrate‐rich layer on the vascular endothelium, and its damage can lead to endothelial and organ dysfunction. Heparanase (HPSE) degrades the eGC in response to cellular stress, but its role in organ dysfunction remains unclear. This study investigates HPSE's role in lung ischemia–reperfusion (I/R) injury. A left lung hilar occlusion model was used in B6 wildtype (WT) and HPSE genetic knockout (−/−) mice to induce I/R injury in vivo. The left lungs were ischemic for 1 h followed by reperfusion for 4 h prior to investigations of lung function and eGC status. Data were compared between uninjured lungs and I/R‐injured lungs in WT and HPSE−/− mice. WT lungs showed significant functional impairment after I/R injury, whereas HPSE−/− lungs did not. Inhibition or knockout of HPSE prevented eGC damage, inflammation, and cellular migration after I/R injury by reducing matrix metalloproteinase activities. HPSE−/− mice exhibited compensatory regulation of related gene expressions. HPSE facilitates eGC degradation leading to inflammation and impaired lung function after I/R injury. HPSE may be a therapeutic target to attenuate graft damage in lung transplantation. [ABSTRACT FROM AUTHOR]

BackgroundObjectiveMethodsResultsConclusionIntegrating aerobic exercise (AE) into rehabilitation programs for post-stroke individuals could enhance motor recovery and cardiovascular health by increasing brain-derived neurotrophic factor (BDNF) and the myokine irisin. Chronic stroke survivors typically exhibit elevated matrix metalloproteinase-9 (MMP-9) activity, which is negatively correlated with steps and time in medium cadence, although the impact of AE on this biomarker remains unclear.To evaluate the effect of high-intensity AE training prior to modified constraint-induced movement therapy (mCIMT) on BDNF and irisin concentration, and on MMP-2 and MMP-9 activity in chronic post-stroke individuals and to associate these results with functional improvements.Nine participants received AE combined with mCIMT for two weeks, while the control group (n = 7) received mCIMT alone. Manual dexterity and functional capacity were assessed before and after the intervention. Serum samples were analyzed for BDNF, irisin, MMP-2 and MMP-9.There were no significant main effects of assessment, group or interaction on molecular biomarkers. However, the AE group had a significant increase in MMP-9 activity post-intervention (p = .033; d = 0.67). For the Box and Block Test, there were significant main effects of assessment (F [1, 14] = 33.27, p = .000, ηp2 = 0.70) and group (F [1, 14] = 5.43, p = .035, ηp2 = .28). No correlations were found between biomarkers and clinical assessments.AE prior to mCIMT did not influence circulating BDNF and irisin levels but did induce an acute rise in MMP-9 activity, suggesting potential effects on cardiovascular remodeling in this population. [ABSTRACT FROM AUTHOR]

Circulating biomarkers have been proposed for early identification of aortic dilatation progression associated with bicuspid aortic valve (BAV), but matrix metalloproteinases (MMPs) are distinguished as signatures of increased extracellular matrix degradation, a landmark of aneurysm formation. The current study aims to identify the role of MMP-1, MMP-2, MMP-9, and the MMP inhibitor, TIMP-1, in identifying aortic dilation in children with BAV. We conducted a study on 73 children divided into two study groups, depending on the presence of aortic dilatation (group 1–43 BAV controls and group 2–30 children with BAV and aortic dilatation). Each patient underwent a cardiac ultrasound and, in each case, serum MMP-1, MMP-2, MMP-9, and TIMP-1 were quantified using xMAP technology. Comparison of the MMPs between the two study groups revealed significantly higher values only in the case of TIMP-1, among BAV controls. Moreover, the same TIMP-1 inversely correlated with aortic annulus absolute size and z score, as well as with ascending aorta z score. No particular correlation between the aortic phenotype and the presence of aortic dilatation was found. Future longitudinal research starting at pediatric ages could show the significance of MMPs screening in BAV individuals as predictors of aortic aneurysm formation. [ABSTRACT FROM AUTHOR]

Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered as a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and β-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and aetiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulphide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling. [ABSTRACT FROM AUTHOR]

In goldfish, spinal cord injury triggers the formation of a fibrous scar at the injury site. Regenerating axons are able to penetrate the scar tissue, resulting in the recovery of motor function. Previous findings suggested that regenerating axons enter the scar through tubular structures surrounded by glial elements with laminin-positive basement membranes and that glial processes expressing glial fibrillary acidic protein (GFAP) are associated with axonal regeneration. How glia contribute to promoting axonal regeneration, however, is unknown. Here, we revealed that glial processes expressing vimentin or brain lipid-binding protein (BLBP) also enter the fibrous scar after spinal cord injury in goldfish. Vimentin-positive glial processes were more numerous than GFAP- or BLBP-positive glial processes in the scar tissue. Regenerating axons in the scar tissue were more closely associated with vimentin-positive glial processes than GFAP-positive glial processes. Vimentin-positive glial processes co-expressed matrix metalloproteinase (MMP)-14. Our findings suggest that vimentin-positive glial processes closely associate with regenerating axons through tubular structures entering the scar after spinal cord injury in goldfish. In intact spinal cord, ependymo-radial glial cell bodies express BLBP and their radial processes express vimentin, suggesting that vimentin-positive glial processes derive from migrating ependymo-radial glial cells. MMP-14 expressed in vimentin-positive glial cells and their processes might provide a beneficial environment for axonal regeneration. [ABSTRACT FROM AUTHOR]

In this work, aerial parts of Taraxacum officinale F.H. Wigg. produced in Umbria, Italy, were chemically investigated by solid-phase microextraction/gas chromatography–mass spectrometry (SPME/GC-MS) to describe their volatile profile. The results obtained showed the preponderant presence of monoterpenes, with limonene and 1,8-cineole as the main components. Further analyses by GC/MS after derivatization reaction were performed to characterize the non-volatile fraction highlighting the presence of fatty acids and di- and triterpenic compounds. T. officinale methanol and dichloromethane extracts, first analyzed by HRGC/MS, were investigated to evaluate the antioxidant activity, cytotoxicity, and antiproliferative properties of MDA cells on the breast cancer cell line and MCF 10A normal epithelial cells as well as the antioxidant activity by colorimetric assays. The impact on matrix metalloproteinases MMP-9 and MMP-2 was also explored in 3D cell systems to investigate the extracts' efficacy in reducing cell invasiveness. The extracts tested showed no cytotoxic activity with EC50 > 250 µg/mL on both cell lines. The DPPH assay revealed higher antioxidant activity in the MeOH extract compared with the DCM extract, while the FRAP assay showed a contrasting result, with the DCM extract exhibiting slightly greater antioxidant capacity. After treatment for 24 h with a non-cytotoxic concentration of 500 µg/mL of the tested extracts, gelatin zymography and Western blot analyses demonstrated that both MeOH and DCM extracts influenced the expression of MMP-9 and MMP-2 in MDA cells within the 3D cell model, leading to a significant decrease in the levels of these gelatinases, which are crucial markers of tumor invasiveness. [ABSTRACT FROM AUTHOR]

BACKGROUND: Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia. It has good clinical effects on steroid-induced osteonecrosis of the femoral head, but the mechanism of action is still not fully clear. OBJECTIVE: To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS: Thirty-two New Zealand rabbits were randomly divided into blank group, model group, internal heat-type acupuncture group and shock wave group using a random number table method, with 8 rabbits in each group. The model group, internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin. The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits, once a week, for 20 minutes each time. The shock wave group received shock wave intervention on the buttocks of rabbits, once a week, with 2 000 beats per session. The blank group and model group were not given any treatment. After 4 weeks of intervention, blood samples and bilateral femoral head samples were collected from experimental rabbits. The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA; the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated; the protein expressions of matrix metalloproteinase 2, matrix metalloproteinase 9, matrix metalloproteinase tissue inhibitor 1, and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION: Compared with the blank group, the model rabbits showed reduced food intake, mental fatigue, and decreased activity; compared with the model group, the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment. Compared with the blank group, the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased (P < 0.001), while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group, and the rate of empty bone lacuna was reduced (P < 0.001). The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group (P < 0.05), while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group (P < 0.05). Compared with the blank group, the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased, while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased (P < 0.001); compared with the model group, the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased, while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group (P < 0.001). Overall, these findings indicate that internal heattype acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors, thus treating early steroid-induced osteonecrosis of the femoral head. [ABSTRACT FROM AUTHOR]

Wound healing is a complex dynamic biomechanical process as the body attempts to restore the integrity of traumatized or devitalized tissues. There are four stages of wound of healing that begins with hemostasis followed by inflammation, proliferation and finally weeks later wound remodeling. Full thickness wounds usually are covered with a dressing material after hemostasis, which allows for controlled hydration. We investigated the potential of a visco-liquid hemostat, polyhedral oligomeric silsesquioxane (POSS), for providing hemostasis and to maintain a microenvironment in the wound bed that would maintain moisture content and promote early re-epithelialization. We hypothesized that the hemostatic agent POSS if left in the wound bed would maintain a protective barrier and accelerate wound healing similar to using saline to irrigate the wound to keep the wound moist. We compared the early phase of wound repair (3–7 days) in a porcine full thickness wound model to evaluate the efficacy of the material. Biopsies were taken after 3 and 7 days to determine the acute response of the POSS hemostat or saline on inflammation, cell migration, concentrations of metalloproteinase (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). Accelerated healing was observed in POSS treated wounds by changes in wound contraction, keratinocyte migration, and development of granulation tissue in comparison to saline treated wounds. Increased concentrations at day 3 of MMP-2, MMP-3, and in MMP-1 at day 7 in POSS treated wounds compared to saline coincide with keratinocyte migration observed in the tissue histology and changes in wound contraction. Tissue concentrations of TIMP-1 and TIMP-2 in POSS treated wounds appear to coordinate the sequence of MMP events in the healing tissue. Matrix metalloproteinase-13, a marker for tissue remodeling, was not upregulated in the early wound healing cascade in either POSS or saline treated wounds at 3 or 7 days. Overall, the data suggests POSS treatment contributed to enhanced early cell migration and wound closure compared to saline treatment. [ABSTRACT FROM AUTHOR]

Thoracic aortic dissection (TAD) is a highly lethal disease occurring inside the aortic wall and is characterized by matrix degradation. Matrix metalloproteinases (MMPs) are members of a large endopeptidase family that function in the degradation of the extracellular matrix (ECM) proteins, the maintenance of the ECM, and the regulation of signaling in the aorta. MMPs are found in tissue with their natural inhibitors. Tissue inhibitors of metalloproteinases (TIMPs) are actively involved in both the activation and inhibition of MMPs. The present study was designed to determine the mRNA level gene expression differences of MMP2, MMP9, TIMP2 and TIMP3, which are considered to have an essential role in TAD, in aortic tissue and circulating monocyte cells. For the purpose of the present study, aortic vascular tissue and peripheral blood-derived monocyte cells were obtained from 10 patients with TAD and 10 control individuals. The gene expression levels of targeted genes (MMP2, MMP9, TIMP2 and TIMP3) were examined by droplet digital PCR. In research results, decreased expression of MMP9, TIMP2 and TIMP3 genes (P=0.043, P=0.009 and P=0.028, respectively) and increased ratio of MMP2/TIMP3 (P=0.012) were obtained in the aortic tissue. No changes were observed in terms of gene expression in monocyte cells. When the results obtained were evaluated within the framework of TAD pathogenesis, it was concluded that expression changes in MMP9, TIMP2 and TIMP3 genes may provide a sensitive environment in aortic tissue and may be associated with TAD formation. In addition, since the expression ratios of MMPs and TIMPs may reflect disease development, it was considered that the evaluation of MMPs along with TIMPs may be an appropriate and informative approach for future studies. [ABSTRACT FROM AUTHOR]

Objective: The aim of this in vitro experimental series was to explore the mode of action of a hydrocellular polyurethane foam dressing (HPFD) and how its advanced features support beneficial interactions with the wound bed to address common barriers to wound healing, thus supporting improved clinical outcomes. Method: Multiple in vitro microbiological tests were performed, assessing prevention of bacterial ingress, surface removal of bacteria, bacterial sequestration and retention into the dressing in a clinically relevant environment. Odour molecule concentrations were measured using gas chromatography and further assays explored matrix metalloproteinase (MMP)-9 retention in the dressing using enzyme linked immunosorbent assay. Results: The HPFD demonstrated marked reductions in bioburden levels across multiple tests. These included prevention of bacterial ingress for seven days, removal of surface bacteria and absorption into the dressing. Further tests identified that most bacteria were sequestered into the hyperabsorbent layer (90.5% for Pseudomonas aeruginosa and 89.6% for meticillin-resistant Staphylococcus aureus). Moreover, the majority of bacteria (99.99% for both test organisms) were retained within the dressing, even upon compression. Additional tests demonstrated a marked reduction of odour molecules following incubation with HPFD and total retention of protease MMP-9 within the dressing. Conclusions: Proactive management of the wound environment with an appropriate advanced wound dressing, such as the HPFD examined in these in vitro investigations, can not only help to minimise the barriers to healing, as observed across this test series by direct interaction with the wound bed, but may, as a result, provide an ideal environment for wound progression with minimal disturbance. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-200b-3p has been associated with many tumors, but its involvement in pituitary adenoma is unclear. This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment. Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA. As well, the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay. The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization. Transfection of the miR-200b-3p inhibitor and small interfering-RECK (si-RECK) was verified by qPCR. GH3 cell viability and proliferation were detected using CCK8 and EdU assays. Apoptosis was detected by flow cytometry and western blotting. Wound healing and Transwell assays were used to detect cell migration and invasion. The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments. miR-200b-3p was highly expressed in pituitary tumor tissue. Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis, inhibited invasion and migration, and inhibited the expression of matrix metalloproteinases. Interestingly, miR-200b-3p negatively regulated RECK. The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues. Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors, and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression. In summary, this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK. The findings provide a new target for the treatment of pituitary adenoma. [ABSTRACT FROM AUTHOR]

Introduction: Achieving strong bond strength of adhesive systems to deep dentin is challenging. Various methods to improve bond strength to deep dentin have been investigated. Chlorhexidine (CHX) enhances the longevity of the bond between adhesives and dentin by inhibiting the collagenolytic activity of Matrix Metalloproteinases (MMPs). Benincasa hispida is a natural plant-based functional food containing minerals and vitamins that help prevent osteoporosis and improve bone health. Aim: To evaluate the Microshear Bond Strength (MSBS) of a 10-methacryloyloxydecyl-dihydrogen Phosphate-based (10-MDP) universal adhesive system to coronal dentin with different dentin surface pretreatments, specifically CHX and Benincasa hispida. Materials and Methods: An in-vitro pilot study was conducted at the Department of Conservative Dentistry and Endodontics, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India, from May 2023 to November 2023. Dentin discs (42) were prepared from human mandibular first molars. A standard etch-and-rinse protocol was performed on the discs. The specimens were assigned to different dentin pretreatments: Group-I (no pretreatment), Group-II (CHX) and Group-III (Benincasa hispida). CHX and Benincasa hispida were applied using micro applicator tips. A dentin bonding agent containing 10-MDP (DBA) was applied, photopolymerised and a composite restoration was fabricated. The MSBS to dentin was evaluated using a universal testing machine. The failure patterns were analysed using a stereomicroscope at 10x magnification. One-way Analysis of Variance (ANOVA) and Tukey’s Honestly Significant Difference (HSD) HSD tests were used for statistical analysis, with a significance level set at α=0.05. Results: The mean MSBS values were 24.2732±5.41329 MPa for Group-III, 14.3848±4.23492 MPa for Group-II and 6.9724±3.15837 MPa for Group-I. Pretreatment of dentin with B. hispida resulted in significantly higher MSBS values compared to the other two groups (p

INTRODUCTION. Fluoroquinolones are antibacterial agents associated with adverse drug reactions (ARDs), including aortic lesions; this ARD risk limits the use of fluoroquinolones. Moreover, fluoroquinolones have been reported to induce lesions in other connective tissues (cartilage, tendons), associated with magnesium deficiency.AIM. The study aimed to analyse the effects of magnesium orotate on the thoracic aorta in laboratory rabbits treated with levofloxacin.MATERIALS AND METHODS. The study randomised laboratory rabbits into 3 groups of 10 animals each to receive oral doses of either the carrier solution (control group), or 150 mg/kg/day levofloxacin (levofloxacin group), or 150 mg/ kg/day levofloxacin and 140 mg/kg/day magnesium orotate (levofloxacin/magnesium group). After 14 days of treatment, venous blood samples were taken to determine the serum levels of magnesium, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), as well as MMP-9 to TIMP-1 ratios. The authors conducted morphological and mechanical characterisation of thoracic aorta samples; the mechanical characterisation involved uniaxial tensile testing. Data are presented as the mean and standard deviation values.RESULTS. The study did not detect any changes in the serum MMP-9, TIMP-1, and magnesium levels or in the MMP-9/TIMP-1 ratios. The authors identified foci of moderate elastic fibre fragmentation in the aortic media in 5 of 10 aortic samples from the levofloxacin group, in 1 of 10 samples from the levofloxacin/magnesium group, and in none from the control group (p=0.013). Rabbits from the levofloxacin group had significantly fewer medial elastic membranes than the others (p=0.015; vs the control group: p=0.022), and their elastic mem

Age-related hearing loss (ARHL) is a common disease among the elderly. Although its pathogenesis remains unclear by now, it is widely accepted that ARHL is associated with the degenerative alterations within each component of the cochlea. Extracellular matrix (ECM) plays a crucial role in cochlear structure and function, providing not only structural support but also participating in vital physiological processes including the development, differentiation, survival of auditory sensory cells, and sound perception. ECM is implicated in the pathogenesis of various neurodegenerative diseases, with certain ECM proteins or associated molecules emerging as potential therapeutic targets. However, few research were carried out on ECM in the cochlea and ECM associated molecules in ARHL. This review aims to delineate the composition of ECM in the cochlea, the changes of the main ECM structure in the cochlea such as the tectorial membrane (TM), the basilar membrane (BM) and the spiral ligament (SL) during aging, as well as the role of ECM associated molecules in ARHL. We hope that this review will foster further research into ARHL. [ABSTRACT FROM AUTHOR]

Wound healing is a complex dynamic biomechanical process as the body attempts to restore the integrity of traumatized or devitalized tissues. There are four stages of wound of healing that begins with hemostasis followed by inflammation, proliferation and finally weeks later wound remodeling. Full thickness wounds usually are covered with a dressing material after hemostasis, which allows for controlled hydration. We investigated the potential of a visco-liquid hemostat, polyhedral oligomeric silsesquioxane (POSS), for providing hemostasis and to maintain a microenvironment in the wound bed that would maintain moisture content and promote early re-epithelialization. We hypothesized that the hemostatic agent POSS if left in the wound bed would maintain a protective barrier and accelerate wound healing similar to using saline to irrigate the wound to keep the wound moist. We compared the early phase of wound repair (3–7 days) in a porcine full thickness wound model to evaluate the efficacy of the material. Biopsies were taken after 3 and 7 days to determine the acute response of the POSS hemostat or saline on inflammation, cell migration, concentrations of metalloproteinase (MMPs), and tissue inhibitors of metalloproteinase (TIMPs). Accelerated healing was observed in POSS treated wounds by changes in wound contraction, keratinocyte migration, and development of granulation tissue in comparison to saline treated wounds. Increased concentrations at day 3 of MMP-2, MMP-3, and in MMP-1 at day 7 in POSS treated wounds compared to saline coincide with keratinocyte migration observed in the tissue histology and changes in wound contraction. Tissue concentrations of TIMP-1 and TIMP-2 in POSS treated wounds appear to coordinate the sequence of MMP events in the healing tissue. Matrix metalloproteinase-13, a marker for tissue remodeling, was not upregulated in the early wound healing cascade in either POSS or saline treated wounds at 3 or 7 days. Overall, the data suggests POSS treatment contributed to enhanced early cell migration and wound closure compared to saline treatment.

Abstract Background Matrix metalloproteinases (MMPs) are critical enzymes involved in the remodeling and defense mechanisms of dental pulp tissue. While their role in permanent teeth has been extensively studied, research focusing on MMPs in primary teeth remains limited. This gap highlights the need for further investigations to understand the specific contributions of MMPs to pulpal defense in primary teeth. Moreover, the clinical efficacy of Biodentine as a pulpotomy material in primary teeth warrants further exploration through well-designed studies to establish its success and long-term outcomes in pediatric dentistry. Aim This study aims to compare the expression levels of MMP-2, MMP-8, and MMP-9 in cases of reversible and irreversible pulpitis. Additionally, it seeks to evaluate the clinical success of Mineral Trioxide Aggregate (MTA) and Biodentine when used as pulpotomy agents in primary molars. By analyzing the differential expression of these MMPs, the study will contribute to a better understanding of their role in pulpal inflammation and the potential therapeutic outcomes of MTA and Biodentine in primary molars. Design In this parallel randomized controlled trial, 63 mandibular primary second molars were assigned to two main groups: Group 1, consisting of 42 teeth diagnosed with reversible pulpitis, and Group 2, consisting of 21 teeth diagnosed with irreversible pulpitis. Group 1 was further divided into two randomized subgroups, each containing 21 teeth. The expression levels of MMP-2, MMP-8, and MMP-9 were evaluated in all samples. Pulpotomy treatments were performed using MTA and Biodentine in Group 1. Clinical and radiographic evaluations were conducted over an 18-month follow-up period. Statistical analyses were carried out using The Kolmogorov-Smirnov test, t-test and Fisher’s exact test (p

Abstract Long non-coding RNAs (lncRNAs) have emerged as important players in cancer progression. Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastasis risk or specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNAs and protein-coding genes revealed six distinct gene clusters with one of the upregulated clusters featuring genes associated with cell motility. Upregulation of the expression of lncRNAs linked to cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed using qRT-PCR. Elevated expression of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with poorer prognosis in HNSCC and lung SCC cohorts within TCGA data, respectively. Altogether, these findings uncover a novel set of lncRNAs implicated in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers and as putative therapeutic targets for locally advanced and metastatic cSCC.

Abstract To explore the molecular pathogenesis of pulmonary arterial hypertension (PAH) and identify potential therapeutic targets, we performed transcriptome sequencing of lung tissue from mice with hypoxia-induced pulmonary hypertension. Our Gene Ontology analysis revealed that “extracellular matrix organization” ranked high in the biological process category, and matrix metallopeptidases (MMPs) and other proteases also played important roles in it. Moreover, compared with those in the normoxia group, we confirmed that MMP s expression was upregulated in the hypoxia group, while the hub gene Timp1 was downregulated. Crocin, a natural MMP inhibitor, was found to reduce inflammation, decrease MMPs levels, increase Timp1 expression levels, and attenuate hypoxia-induced pulmonary hypertension in mice. In addition, analysis of the cell distribution of MMPs and Timp1 in the human lung cell atlas using single-cell RNAseq datasets revealed that MMPs and Timp1 are mainly expressed in a population of fibroblasts. Moreover, in vitro experiments revealed that crocin significantly inhibited myofibroblast proliferation, migration, and extracellular matrix deposition. Furthermore, we demonstrated that crocin inhibited TGF-β1-induced fibroblast activation and regulated the pulmonary arterial fibroblast MMP2/TIMP1 balance by inhibiting the TGF-β1/Smad3 signaling pathway. In summary, our results indicate that crocin attenuates hypoxia-induced pulmonary hypertension in mice by inhibiting TGF-β1-induced myofibroblast activation.

Background: Matrix metalloproteinases (MMPs) are critical enzymes involved in the remodeling and defense mechanisms of dental pulp tissue. While their role in permanent teeth has been extensively studied, research focusing on MMPs in primary teeth remains limited. This gap highlights the need for further investigations to understand the specific contributions of MMPs to pulpal defense in primary teeth. Moreover, the clinical efficacy of Biodentine as a pulpotomy material in primary teeth warrants further exploration through well-designed studies to establish its success and long-term outcomes in pediatric dentistry. Aim: This study aims to compare the expression levels of MMP-2, MMP-8, and MMP-9 in cases of reversible and irreversible pulpitis. Additionally, it seeks to evaluate the clinical success of Mineral Trioxide Aggregate (MTA) and Biodentine when used as pulpotomy agents in primary molars. By analyzing the differential expression of these MMPs, the study will contribute to a better understanding of their role in pulpal inflammation and the potential therapeutic outcomes of MTA and Biodentine in primary molars. Design: In this parallel randomized controlled trial, 63 mandibular primary second molars were assigned to two main groups: Group 1, consisting of 42 teeth diagnosed with reversible pulpitis, and Group 2, consisting of 21 teeth diagnosed with irreversible pulpitis. Group 1 was further divided into two randomized subgroups, each containing 21 teeth. The expression levels of MMP-2, MMP-8, and MMP-9 were evaluated in all samples. Pulpotomy treatments were performed using MTA and Biodentine in Group 1. Clinical and radiographic evaluations were conducted over an 18-month follow-up period. Statistical analyses were carried out using The Kolmogorov-Smirnov test, t-test and Fisher's exact test (p < 0.05). Results: The study revealed that MMP-2 and MMP-9 expression levels were significantly elevated in specimens with irreversible pulpitis (p = 0.01), indicating a potential correlation between these matrix metalloproteinases and the severity of pulpal inflammation. However, no significant difference was observed in the clinical success rates of pulpotomies performed with MTA and Biodentine, suggesting that both materials are equally effective in the treatment of primary molars with reversible pulpitis. Conclusions: The expression of MMP-2 and MMP-9 in pulpal blood presents a promising biomarker for assessing the degree of pulpal inflammation in primary teeth, offering a potentially valuable diagnostic tool. Additionally, the clinical success of Biodentine in pulpotomy procedures supports its viability as an effective alternative to MTA, providing a reliable option. Clinical Trial Registration ID: The study protocol has been registered with an ID: NCT05145686. Registration Date: 9th November 2021. [ABSTRACT FROM AUTHOR]

Introduction: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC. Methods: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically. Results: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3−54] versus 6 [3−25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2. Conclusion: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. Methods: MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. Results: Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH (p < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. Conclusions: While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects. [ABSTRACT FROM AUTHOR]

Aortic aneurysm/ dissection is the primary cause of mortality in patients with Marfan syndrome (MFS). Though aberrant activation of the transforming growth factor-β(TGF-β) pathway has been considered the central pathogenic mechanism for MFS aortic aneurysms, recent research has gradually revealed the involvement of other signaling pathways in MFS. This review summarizes the latest researches on the molecular mechanisms of MFS, including classical TGF-β and related signaling pathways such as Notch and nitric oxide(NO), as well as epigenetics and gene therapy, which provide new insights for the prevention and treatment of MFS. [ABSTRACT FROM AUTHOR]

The ovary generally undergoes tissue remodeling during larval to pupal transition, which includes membrane degeneration and ovariole growth. At the same time, the hormones produced by insects significantly change during metamorphosis. However, the regulatory mechanism for ovarian development and hormones is not fully understood in insects. Herein, we found that matrix metalloproteinase 2 (MMP2) was highly expressed in the ovarian capsules and ovarioles, and the development was abnormal after knocking out MMP2 in Bombyx mori. The process of abnormal degradation of collagen I due to MMP2 deletion, which resulted in abnormal development of ovarioles and eggs, was analyzed in detail. The proteomics of ovaries in the MMP2‐knock out and wild type strains showed a critically significant difference in the expression of a protein, insulin‐like peptide (ILP). Additional analysis revealed significant alteration of ILP during ovarian development, and abnormal expression of ILP significantly affected ovarian development in vivo and MMP2 expression in vitro and in vivo. These results showed that MMP2 regulation of ovarian tissue remodeling is closely related to ILP expression. Our study provides new insights into the regulatory mechanism of MMP2 and ovarian development in B. mori. [ABSTRACT FROM AUTHOR]

Cerebral stroke is ranked as the third most common contributor to global mortality and disability. The involvement of inflammatory mechanisms, both peripherally and within the CNS, holds significance in the pathophysiological cascades following the initiation of stroke. After the onset of acute stroke, predominantly ischemic, a subsequent phase of neuroinflammation ensues. It is a dual-effect process that not only exacerbates injury, leading to cell death, but paradoxically, it also serves a shielding role in facilitating recovery. Cytokines serve as pivotal mediators within the inflammatory cascade, actively contributing to the progression of ischemic damage. Stroke is followed by increased expression of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, etc. leading to the recruitment and stimulation of glial cells and peripheral leukocytes at the site of injury, promoting neuroinflammation. Cytokines can directly induce neuronal injury and death through various mechanisms, including excitotoxicity, oxidative stress, HPA-axis activation, secretion of matrix metalloproteinase and apoptosis. They can also amplify the inflammatory response, leading to further neuronal damage. Therapeutic strategies aimed at modulating cytokine release, immune response and cytokine signalling or activity are being explored as potential interventions to mitigate neuroinflammation and its detrimental effects in stroke. In this review, we have given a concise summary of our current knowledge of the function of various cytokines, brain inflammation and various signalling and molecular pathways including JAK/STAT3, TGF-β/Smad, MAPK, HMGB1/TLR and NF-κB modulated cytokines regulation in stroke. Therapeutic agents such as MCC950, genistein, edaravone, minocycline, etc. targeting various cytokines-associated signalling pathways have shown efficacy in preclinical and clinical trials reducing the pathophysiology of the illness were also addressed in this study. [Display omitted] • The onset of stroke initiates inflammatory cascades within the cerebral milieu. • Cytokines are the major culprit behind neuroinflammation in ischemic stroke. • Excitotoxicity and oxidative stress fuel neuroinflammation in stroke. • NLRP3, S1PR, HMGB1/TLR/NFκB play a crucial role in stroke progression. • Drugs targeting these pathways may alleviate stroke pathology. [ABSTRACT FROM AUTHOR]

Autoimmune diseases hold significant importance in the realm of medical research, prompting a thorough exploration of potential therapeutic interventions. One crucial aspect of this exploration involves understanding the intricate processes of histone acetylation and deacetylation. Histone acetylation, facilitated by histone acetyl transferases (HATs), is instrumental in rendering DNA transcriptionally active. Conversely, histone deacetylases (HDACs) are responsible for the removal of acetyl groups, influencing gene expression regulation. The upregulation of HDACs, observed in various cancers, has steered attention towards histone deacetylase inhibitors (HDACi) as promising anti-cancer agents. Beyond cancer, HDACi has demonstrated anti-inflammatory properties, prompting interest in their potential therapeutic applications for inflammatory diseases such as rheumatoid arthritis (RA). RA, characterized by the immune system erroneously attacking healthy cells, leads to joint inflammation. Recent studies suggest that HDACi could offer a viable therapeutic strategy for RA, with potential mechanisms including the inhibition of synovial tissue growth and suppression of pro-inflammatory cytokines. Furthermore, HDACi may exert protective effects on bone and cartilage, common targets in RA pathology. In-depth investigations through in vivo and histopathology studies contribute to the ongoing discourse on the therapeutic benefits of HDACis in the context of RA treatment. [ABSTRACT FROM AUTHOR]

Osimertinib induces a marked response in non–small‐cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) gene mutations. However, acquired resistance to osimertinib remains an inevitable problem. In this study, we aimed to investigate osimertinib‐resistant mechanisms and evaluate the combination therapy of afatinib and chemotherapy. We established osimertinib‐resistant cell lines (PC‐9‐OR and H1975‐OR) from EGFR‐mutant lung adenocarcinoma cell lines PC‐9 and H1975 by high exposure and stepwise method. Combination therapy of afatinib plus carboplatin (CBDCA) and pemetrexed (PEM) was effective in both parental and osimertinib‐resistant cells. We found that expression of thrombospondin‐1 (TSP‐1) was upregulated in resistant cells using cDNA microarray analysis. We demonstrated that TSP‐1 increases the expression of matrix metalloproteinases through integrin signaling and promotes tumor invasion in both PC‐9‐OR and H1975‐OR, and that epithelial‐to‐mesenchymal transition (EMT) was involved in H1975‐OR. Afatinib plus CBDCA and PEM reversed TSP‐1‐induced invasion ability and EMT changes in resistant cells. In PC‐9‐OR xenograft mouse models (five female Balb/c‐Nude mice in each group), combination therapy strongly inhibited tumor growth compared with afatinib monotherapy (5 mg/kg, orally, five times per week) or CBDCA (75 mg/kg, intraperitoneally, one time per week) + PEM (100 mg/kg, intraperitoneally, one time per week) over a 28‐day period. These results suggest that the combination of afatinib plus CBDCA and PEM, which effectively suppresses TSP‐1 expression, may be a promising option in EGFR‐mutated NSCLC patients after the acquisition of osimertinib resistance. [ABSTRACT FROM AUTHOR]

High mortality rate of melanoma is due to the metastasis of malignant cells. Galbanic acid (GBA) is a natural sesquiterpene coumarin with valuable pharmaceutical activities. Our study aimed to investigate whether GBA can affect the migration, invasion, and adhesion of melanoma cells. The survival rate of B16F10 cells was measured using the alamarBlue assay. Scratch, adhesion, and invasion assays were performed to determine the effect of GBA on metastatic behavior of cells. Moreover, gelatin zymography was done to assess the activity of MMP-2 and MMP-9, and qRT-PCR was used to investigate the effect of GBA on the expression of candidate genes. Based on the results of alamarBlue assay, 40 µM GBA was chosen as the optimum concentration for all tests. Our findings indicated that GBA significantly decreased the invasion and migration of B16F10 cells while enhancing their adhesion ability. In addition, gelatin zymography demonstrated that GBA reduced the enzymatic activity of MMP-2 and MMP-9. Moreover, qRT-PCR revealed that GBA reduced the expression of N-cadherin and fibronectin. Current findings demonstrated, for the first time, that GBA inhibited the migration and invasion of melanoma cells via reducing the activity of MMP-2 and MMP-9 and downregulating N-cadherin and fibronectin expression. Accordingly, GBA could be suggested as a potential therapeutic agent for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have emerged as important players in cancer progression. Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastasis risk or specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNAs and protein-coding genes revealed six distinct gene clusters with one of the upregulated clusters featuring genes associated with cell motility. Upregulation of the expression of lncRNAs linked to cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed using qRT-PCR. Elevated expression of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with poorer prognosis in HNSCC and lung SCC cohorts within TCGA data, respectively. Altogether, these findings uncover a novel set of lncRNAs implicated in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers and as putative therapeutic targets for locally advanced and metastatic cSCC. [ABSTRACT FROM AUTHOR]

Objective To observe the effect of curcumin on the expression of matrix metalloproteinase （MMP） and fibronectin 1（FN1） in human retinal pigment epithelium （RPE）. Methods Human RPE cells were divided into two groups: the curcumin group and control group; cells in the curcumin group were added with 0.5×10-5 mol/L curcumin, and cells in the control group were not treated with curcumin. After cells of the two groups were continuously incubated for 48 h, real-time fluorescence quantitative PCR was used to detect the matrix metalloproteinase (MMP) 1, MMP2, MMP3, MMP9, and FN1 mRNAs, and Western blotting was used to detect the MMP1, MMP2, MMP3, MMP9, FN1 proteins in cells. Results The relative expression levels of MMP1, MMP2, MMP3, MMP9, and FN1 mRNAs in cells in the curcumin group were 0. 41 ± 0. 14, 5. 020. 22, 1. 090. 21, 0. 470. 28, and 2. 500. 21, and those in the control group were 5. 100. 38, 6. 430. 15, 0. 270. 19, 1. 820. 12, and 6. 830. 18, respectively, with statistically significant differences between these two groups （all P<0. 05）. The relative expression levels of MMP1, MMP2, MMP3, MMP9, and FN1 proteins were 6 155. 33124. 01, 6 208. 00157. 33, 8 126. 33235. 78, 3 541. 67 130. 16, 3 684. 3390. 22, respectively, in the curcumin group, versus 16 207. 33210. 19, 8 053. 3361. 98, 2 543. 67122. 20, 9 477. 33108. 68, and 8 218. 00239. 86, respectively, in the control group, with statistically significant differences between these two groups （all P<0. 05）. Conclusion Curcumin up-regulates the expression of MMP1, MMP2, MMP9, FN1 and down-regulates the expression of MMP3 in human RPE cells [ABSTRACT FROM AUTHOR]

Liposomes carrying chemotherapeutic drugs can accumulate passively in solid tumors at high levels. However, additional targeting of the liposomes towards e.g. receptors expressed on cancer cells may improve their interaction and therapeutic properties. In this study, we designed a liposomal delivery system, which utilizes the intrinsic characteristics of HER2-positive tumors to ensure efficient delivery of oxaliplatin to the cancer cells. On the liposome surface, trastuzumab, an antibody specific to the HER2 receptor, was shown to facilitate internalization by the cancer cells. A polyethylene glycol (PEG) layer on the liposome surface provides protection from mononuclear phagocyte system uptake. To optimize the interaction between liposomes and cancer cells, a protease-sensitive cleavable peptide linker was inserted at the base of each PEG. The PEG layer is then cleaved off by intra- and extracellular matrix metalloproteinases (MMPs) upon accumulation in the tumor. Our data demonstrate that the removal of PEG significantly destabilizes the liposomes and leads to substantial oxaliplatin release. The proposed beneficial effect of combining antibody-mediated internalization with MMP sensitivity was confirmed in a series of in vivo studies using ovarian cancer xenograft models. The results demonstrated that HER2-targeted MMP-sensitive liposomes have superior anticancer activity compared to non-targeted and non-cleavable liposomes. [Display omitted] • We have designed enzyme-activated liposomes targeted at HER2-positive cancers. • The liposomes are readily internalized by HER2-positive cancer cells. • In the presence of enzymes expressed by tumors, the liposomes release their cargo. • These liposomes have superior in vivo efficacy compared to control liposomes. • Our liposomes are promising as a treatment for HER2-positive cancer. [ABSTRACT FROM AUTHOR]

Enhancing the durability of the adhesive--dentin interface is regarded as one of the main goals of contemporary adhesive dentistry. This study aimed to evaluate the effect of plasma pretreatment on MMP-2 inhibition and on the immediate and delayed shear bond strength of a universal adhesive used in 'etch-and-rinse' or 'self-etch' mode. Sixty-four decoronated human maxillary premolars were used for the bond strength test, while sixty-four dentin beams (1 mm thick, 2 mm wide, and 6 mm long) were used for the MMP-2 inhibition test. The specimens in each study were divided into four main groups (n=16): Group A: the universal adhesive (G-Premio bond) used in the 'etch-and-rinse' mode. Group B: as Group A but with plasma treatment prior to adhesive application. Group C: the universal adhesive used in 'self-etch' mode. Group D: as Group C but with plasma treatment prior to adhesive application. Each group was further subdivided into two subgroups (I and II) aged for 24 hours or 6 months, respectively. The universal adhesive was applied following the manufacturer's instructions. Nonthermal plasma was applied using a PiezoBrush® PZ3 Handheld Device. A universal composite was then applied in all of the groups. The shear bond strength test was carried out using a universal testing machine, while the MMP-2 concentration was measured using a special ELISA kit. Statistical Analysis: The data were analysed using one-way ANOVA, Tukey's HSD test, or an independent sample t test at a significance level of 0.05. The highest mean value of shear bond strength (SBS) was recorded for Group BII (30.12 ± 2.29 MPa), while the lowest mean value was recorded for Group CII (12.25 ± 0.88 MPa). Significant differences were found between each set of aged subgroups, except for C1/D1, CII/DII, CI/CII and DI/DII. For MMP-2, the highest mean value was recorded for Group AI (0.483 ng/ml), while the lowest mean value was recorded for Group BII (0.086 ng/ml). Significant differences were found between each set of aged subgroups, except for C1/CII. Plasma pretreatment of an etched dentin surface prior to universal adhesive application seems to be a promising protocol for increasing the longevity of bonded composite restorations, as it significantly increased the SBS after six months of ageing. [ABSTRACT FROM AUTHOR]

Bacterial products, host immune cells and cytokines have been reported to play an important role in the pathogenesis of apical periodontitis (AP). This study aimed to determine the main bacterial species in the microbiota as gram positive and negative and to compare the relationship between matrix metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-α with controlled patient groups. 60 patients with AP and extraction indication were included in the study. 30 systemically healthy volunteers without AP were selected as the control group. After access cavity preparation, an initial microbiologic sample (S1) was taken from the root canal. After atraumatic extraction of the tooth, a second microbial sample (S2) was taken from the extraradicular region. After bacterial DNA extraction, 16S rRNA gene primer was designed for sequence analysis. Bacterial community profiling was made by Sanger sequencing of the PCR products. In addition, serum MMP-9 and TNF-α levels were measured from all patients. TNF-α levels of the AP group were higher than the control group, while MMP-9 levels were found to be lower (p = 0.0264 and p = 0.0146, respectively). There was no difference in the main bacterial species isolated from the samples taken from the intracanal and extraradicular region of the tooth with AP (p = 0.714). The main bacterial species in the intracanal region of the tooth with AP are similar to the main bacterial species in the extraradicular region. The pathophysiology of the tooth with AP is associated with low MMP-9 and high TNF-α, independent of the bacterial species in the intracanal and extraradicular regions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Collagen is the most abundant extracellular matrix component, which is closely related to the structure and function of the extracellular matrix of skeletal muscle, but the effect and mechanism of recombinant human collagen (rhC) produced by bioengineering technology on the extracellular matrix of skeletal muscle are unclear. OBJECTIVE: To investigate the effect of rhC supplementation on the remodeling of skeletal muscle extracellular matrix after eccentric exercise, thereby revealing the possible mechanism by which rhC improves the injury of skeletal muscle extracellular matrix and promote the recovery after exercise. METHODS: A total of 104 healthy male C57 mice aged 8 weeks old were randomly divided into control group (normal saline), low-dose rhC group (0.2 g/kg), medium-dose rhC group (1.0 g/kg), and high-dose rhC group (2.0 g/kg). Two mice in each group were selected after continuous 7 days of intragastric intervention, and organs were dissected for hematoxylin-eosin staining to determine inflammatory infiltrates. On the 8th day, the remaining mice were subjected to eccentric exercise. The structural changes of the skeletal muscle extracellular matrix were observed under scanning electron microscopy immediately (0), 24, 48, and 96 hours after eccentric exercise. Meanwhile, grip strength, creatine kinase activity, and protein levels of matrix metalloproteinases 2, 9, 14 and tissue inhibitor of metalloproteinase-2 in skeletal muscle were detected by western blot assay. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results indicated that short-term rhC supplementation showed no significant effects on the morphology of the heart, liver, spleen and kidney. After one-time eccentric exercise, the recovery rate of grip strength in the medium- and high-dose rhC groups was significantly increased (P < 0.01). The trend of creatine kinase changes was consistent in all groups and there was no significant difference between groups. The recovery process of the extracellular matrix in the low-dose rhC group was faster than that in the control group, and the muscle tract membrane in the medium- and high-dose rhC groups was more complete. The protein level of matrix metalloproteinase 9 in the high-dose rhC group was significantly decreased (P < 0.05). The protein levels of matrix metalloproteinase 14 in the medium- and high-dose rhC groups were significantly decreased (P < 0.05). The protein levels of matrix metalloproteinase 2 in the medium- and high-dose rhC groups were significantly decreased (P < 0.05). Tissue inhibitor of metalloproteinase-2 protein levels in the medium- and high-dose rhC groups were significantly increased (P < 0.05). The ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase-2 in each rhC group was significantly decreased (P < 0.05). To conclude, pre-supplementation of 1.0 and 2.0 g/kg rhC for 7 days can inhibit extracellular matrix degradation in skeletal muscle after exercise by modulating matrix metalloproteinases and matrix metalloproteinase inhibitors, thereby promoting recovery of skeletal muscle strength in mice. [ABSTRACT FROM AUTHOR]

During the pupal‐adult eclosion process of holometabolous insects, the old cuticle is shed and replaced by a completely different new cuticle that requires tanning and expansion, along with extensive extracellular matrix (ECM) remodeling. In vertebrates, matrix metalloproteinases (MMPs), a class of zinc‐dependent endopeptidases, play key roles in regulating the ECM that surrounds cells. However, little is known about these extracellular proteinases available in insects. The small hive beetle (SHB), Aethina tumida, is a widespread invasive parasite of honey bees. In this study, 6 MMP homologs were identified in the SHB genome. RNA interference experiments showed that all 6 AtMmps are not required for the larval‐pupal transition, only AtMmp2 was essential for pupal‐adult eclosion in SHB. Knockdown of AtMmp2 resulted in eclosion defects and wing expansion failure, as well as mortality within 3 d of adult eclosion. Transcriptomic analysis revealed that knockdown of AtMmp2 significantly increased expression of the Toll and Imd pathways, chitin metabolism, and cross‐linking (such as the pro‐phenoloxidase activating cascade pathway and the tyrosine‐mediated cuticle sclerotization and pigmentation pathway). These data revealed evolutionarily conserved functions of Mmp2 in controlling adult eclosion and wing expansion, also provided a preliminary exploration of the novel function of regulating Toll and Imd pathways, as well as new insights into how MMPs regulate insect development and defense barriers. [ABSTRACT FROM AUTHOR]

Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe−/− mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe−/− mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans. [ABSTRACT FROM AUTHOR]

The pericellular matrix (PCM) serves a critical role in signal transduction and mechanoprotection in chondrocytes. Osteoarthritis (OA) leads to a gradual deterioration of the cartilage, marked by a shift in the spatial arrangement of chondrocytes from initially isolated strands to large cell clusters in end-stage degeneration. These changes coincide with progressive enzymatic breakdown of the PCM. This study aims to assess the role and involvement of specific matrix metalloproteinases (MMPs) in PCM degradation during OA. We selected cartilage samples from 148 OA patients based on the predominant spatial chondrocyte patterns. The presence of various MMPs (-1,-2,-3,-7,-8,-9,-10,-12,-13) was identified by multiplexed immunoassays. For each pattern and identified MMP, the levels and activation states (pro-form vs. active form) were measured by zymograms and western blots. The localization of these MMPs was determined using immunohistochemical labeling. To verify these results, healthy cartilage was exposed to purified MMPs, and the consecutive structural integrity of the PCM was analyzed through immunolabeling and proximity ligation assay. Screening showed elevated levels of MMP-1,-2,-3,-7, and -13, with their expression profile showing a clear dependency of the degeneration stage. MMP-2 and -7 were localized in the PCM, whereas MMP-1,-7, and -13 were predominantly intracellular. We found that MMP-2 and -3 directly disrupt collagen type VI, and MMP-3 and -7 destroy perlecan. MMP-2, -3, and -7 emerge as central players in early PCM degradation in OA. With the disease's initial stages already displaying elevated peaks in MMP expression, this insight may guide early targeted therapies to halt abnormal PCM remodeling. Osteoarthritis (OA) causes a gradual deterioration of the articular cartilage, accompanied by a progressive breakdown of the pericellular matrix (PCM). The PCM's crucial function in protecting and transmitting signals within chondrocytes is impaired in OA. By studying 148 OA-patient cartilage samples, the involvement of matrix metalloproteinases (MMPs) in PCM breakdown was explored. Findings highlighted elevated levels of certain MMPs linked to different stages of degeneration. Notably, MMP-2, -3, and -7 were identified as potent contributors to early PCM degradation, disrupting key components like collagen type VI and perlecan. Understanding these MMPs' roles in initiating OA progression, especially in its early stages, provides insights into potential targets for interventions to preserve PCM integrity and potentially impeding OA advancement. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. Methods: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. Results: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. Conclusions: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) caused by external mechanical forces is a major health burden worldwide, but the underlying mechanism in glia remains largely unclear. We report herein that Drosophila adults exhibit a defective blood–brain barrier, elevated innate immune responses, and astrocyte swelling upon consecutive strikes with a high-impact trauma device. RNA sequencing (RNA-seq) analysis of these astrocytes revealed upregulated expression of genes encoding PDGF and VEGF receptor-related (Pvr, a receptor tyrosine kinase), adaptor protein complex 1 (AP-1, a transcription factor complex of the c-Jun N-terminal kinase pathway) composed of Jun-related antigen (Jra) and kayak (kay), and matrix metalloproteinase 1 (Mmp1) following TBI. Interestingly, Pvr is both required and sufficient for AP-1 and Mmp1 upregulation, while knockdown of AP-1 expression in the background of Pvr overexpression in astrocytes rescued Mmp1 upregulation upon TBI, indicating that Pvr acts as the upstream receptor for the downstream AP-1–Mmp1 transduction. Moreover, dynamin-associated endocytosis was found to be an important regulatory step in downregulating Pvr signaling. Our results identify a new Pvr–AP-1–Mmp1 signaling pathway in astrocytes in response to TBI, providing potential targets for developing new therapeutic strategies for TBI.

Abstract The endothelial glycocalyx (eGC) is a carbohydrate‐rich layer on the vascular endothelium, and its damage can lead to endothelial and organ dysfunction. Heparanase (HPSE) degrades the eGC in response to cellular stress, but its role in organ dysfunction remains unclear. This study investigates HPSE's role in lung ischemia–reperfusion (I/R) injury. A left lung hilar occlusion model was used in B6 wildtype (WT) and HPSE genetic knockout (−/−) mice to induce I/R injury in vivo. The left lungs were ischemic for 1 h followed by reperfusion for 4 h prior to investigations of lung function and eGC status. Data were compared between uninjured lungs and I/R‐injured lungs in WT and HPSE−/− mice. WT lungs showed significant functional impairment after I/R injury, whereas HPSE−/− lungs did not. Inhibition or knockout of HPSE prevented eGC damage, inflammation, and cellular migration after I/R injury by reducing matrix metalloproteinase activities. HPSE−/− mice exhibited compensatory regulation of related gene expressions. HPSE facilitates eGC degradation leading to inflammation and impaired lung function after I/R injury. HPSE may be a therapeutic target to attenuate graft damage in lung transplantation.

Abstract Background Managing polytrauma victims poses a significant challenge to clinicians since applying the same therapy to patients with similar injury patterns may result in different outcomes. Using serum biomarkers hopefully allows for treating each multiple injured in the best possible individual way. Since matrix metalloproteinases (MMPs) play pivotal roles in various physiological processes, they might be a reliable tool in polytrauma care. Methods We evaluated 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and stayed at the intensive care unit for at least one night. We determined their MMP3, MMP8, MMP9, MMP10, MMP12, and MMP13 serum levels at admission (day 0) and on days 1, 3, 5, 7, and 10. Results Median MMP8, MMP9, and MMP12 levels immediately rose after the polytrauma occurred; however, they significantly decreased from admission to day 1 and significantly increased from day 1 to day 10, showing similar time trajectories and (very) strong correlations between each two of the three enzyme levels assessed at the same measurement point. For a two-day lag, autocorrelations were significant for MMP8 (− 0.512) and MMP9 (− 0.302) and for cross-correlations between MMP8 and MMP9 (− 0.439), MMP8 and MMP12 (− 0.416), and MMP9 and MMP12 (− 0.307). Moreover, median MMP3, MMP10, and MMP13 levels significantly increased from admission to day 3 and significantly decreased from day 3 to day 10, showing similar time trajectories and an (almost) strong association between every 2 levels until day 7. Significant cross-correlations were detected between MMP3 and MMP10 (0.414) and MMP13 and MMP10 (0.362). Finally, the MMP10 day 0 level was identified as a predictor for in-hospital mortality. Any increase of the MMP10 level by 200 pg/mL decreased the odds of dying by 28.5%. Conclusions The time trajectories of the highly varying individual MMP levels elucidate the involvement of these enzymes in the endogenous defense response following polytrauma. Similar time courses of MMP levels might indicate similar injury causes, whereas lead–lag effects reveal causative relations between several enzyme pairs. Finally, MMP10 abundantly released into circulation after polytrauma might have a protective effect against dying.

Protecting the skin from the effects of UVB radiation using natural products is crucial in the cosmeceutical industry. This study aims to investigate the protective effects of Bangle (Zingiber cassumunar Roxb.) against UVB‐induced skin damage in Wistar albino rats. The rhizomes were macerated using 70% ethanol v/v, followed by n‐hexane to obtain n‐hexane soluble and n‐hexane insoluble fraction. The antioxidant properties of the ethanol extracts and n‐hexane soluble fraction were evaluated using a 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay. The study also examined the antiphotoaging properties through reactive oxygen species (ROS) scavenging assay, matrix metalloproteinase‐1 (MMP‐1) expression, and tyrosinase expression against UVB radiation in Wistar albino rats. The results demonstrated that the Z. cassumunar extract and fraction effectively converted DPPH radicals into a more stable compound. Analysis revealed the presence of Benzene, 4‐(1Z)‐1,3‐butadien‐1‐yl‐1,2‐dimethoxy‐ and (E)‐4‐(3,4‐Dimethoxyphenyl) but‐3‐en‐1‐ol as the primary compounds in both the extract and fraction, suggesting their contribution to the observed activity. Furthermore, Z. cassumunar compounds could reduce UVB‐induced ROS production and may protect against skin photoaging by changing the expression of MMP‐1 and tyrosinase levels in Wistar albino rats. These findings suggest that Z. cassumunar holds promise for preventing skin aging.

BackgroundPermethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. ObjectiveTo observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. MethodsHMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. ResultsHMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P

Objective: Osteoarthritis (OA) as a common musculoskeletal disorder is the main cause of disability in the world. The present study aimed to evaluate the effects of pomegranate peel extract (PPE) on some inflammatory markers and matrix maloproteinase1 (MMP1) in women with knee OA. Methods: Sixty obese women with knee OA aged 38 to 60 years were included in this clinical trial. The women were allocated into intervention (n = 30) and placebo (n = 30) groups along with standard drug therapy receiving 500 mg PPE or placebo twice daily for 8 weeks, respectively. Three-day food records, anthropometric measurements, fasting blood samples, and physical activity questionnaires were gathered at the baseline and the end of the study. Results: The supplementation of PPE significantly reduced the serum high-sensitivity C-reactive protein (hs-CRP), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), MMP1, and monocyte chemoattractant protein-1 (MCP-1) levels of the patients within the intervened group (all, P <.05) and compared with the placebo (P =.002,.045,.040, and.003, respectively) at the end of the study. The serum NF-ĸB levels significantly increased within the placebo group at the end of the trial (P =.002). Changes in other variables in the placebo group were not significant (P >.05). Conclusions: The findings of this clinical trial indicated that PPE supplementation decreased serum inflammatory markers including hs-CRP, NF-ĸB, and MCP-1 and MMP1 levels in women with knee OA. PPE supplementation may be useful as a part of an integrated approach to modulating inflammatory complications in women with knee OA. [ABSTRACT FROM AUTHOR]