Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

Identification of lignans as selective cyclooxygenase-2 inhibitors from the extract of Acanthopanacis cortex.

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6-8 and 13-16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

A novel in vitro cell model of the proteinase/antiproteinase balance observed in alpha-1 antitrypsin deficiency.

Background: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting from mutations in the alpha-1 antitrypsin (AAT) protein, a major systemic antiproteinase, resulting in reduced/no release of AAT, disrupting the proteinase/antiproteinase balance. A sustained imbalance can cause structural changes to the lung parenchyma, leading to emphysema. Predicting and assessing human responses to potential therapeutic candidates from preclinical animal studies have been challenging. Our aims were to develop a more physiologically relevant in vitro model of the proteinase/antiproteinase balance and assess whether the data generated could better predict the efficacy of pharmacological candidates to inform decisions on clinical trials, together with expected biomarker responses. Methods: We developed an in vitro model assessing the proteinase/antiproteinase balance by the changes in the fibrinogen cleavage products of neutrophil elastase (NE) and proteinase 3 (PR3). This allowed the assessment of physiological and pharmaceutical neutrophil serine proteinase (NSP) inhibitors to determine the putative threshold at which the maximal effect is achieved. Results: AAT significantly reduced NE and PR3 activity footprints, with the maximal reduction achieved at concentrations above 10 µM. The inhibitor MPH966 alone also significantly reduced NE footprint generation in a concentration-dependent manner, leveling out above 100 nM but had no effect on the PR3 footprint. At levels of AAT consistent with AATD, MPH966 had an additive effect, reducing the NE activity footprint more than either inhibitor alone. Conclusion: Our results support an inhibitor threshold above which the activity footprint generation appears resistant to increasing dosage. Our model can support the testing of inhibitors, confirming activity biomarkers as indicators of likely pharmaceutical efficacy, the assessment of NSP activity in the pathophysiology of emphysema, and the likely function of biological or pharmacological inhibitors in disease management.

Blocking HXA3-mediated neutrophil elastase release during S. pneumoniae lung infection limits pulmonary epithelial barrier disruption and bacteremia.

Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant three-fold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin (PLY), triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive lipids, including hepoxilin A3 (HXA3), a hydroxy epoxide PMN chemoattractant that has been hypothesized to facilitate breach of mucosal barriers. To understand how 12-LOX-dependent inflammation promotes dissemination during Sp lung infection and dissemination, we utilized bronchial stem cell-derived air-liquid interface (ALI) cultures that lack this enzyme to show that HXA3 methyl ester (HXA3-ME) is sufficient to promote basolateral-to-apical PMN transmigration, monolayer disruption, and concomitant Sp barrier breach. In contrast, PMN transmigration in response to the non-eicosanoid chemoattractant fMLP did not lead to epithelial disruption or bacterial translocation. Correspondingly, HXA3-ME but not fMLP increased release of neutrophil elastase (NE) from Sp-infected PMNs. Pharmacologic blockade of NE secretion or activity diminished epithelial barrier disruption and bacteremia after pulmonary challenge of mice. Thus, HXA3 promotes barrier disrupting PMN transmigration and NE release, pathological events that can be targeted to curtail systemic disease following pneumococcal pneumonia.

Alpha-1 antitrypsin targeted neutrophil elastase protects against sepsis-induced inflammation and coagulation in mice via inhibiting neutrophil extracellular trap formation.

AIMS: Sepsis pathophysiology is complex and identifying effective treatments for sepsis remains challenging. The study aims to identify effective drugs and targets for sepsis through transcriptomic analysis of sepsis patients, repositioning analysis of compounds, and validation by animal models. MAIN METHODS: GSE185263 obtained from the GEO database that includes gene expression profiles of 44 healthy controls and 348 sepsis patients categorized by severity. Bioinformatic algorithms revealed the molecular, function, and immune characteristics of the sepsis, and constructed sepsis-related protein-protein interaction networks. Subsequently, Random Walk with Restart analysis was applied to identify candidate drugs for sepsis, which were tested in animal models for survival, inflammation, coagulation, and multi-organ damage. KEY FINDINGS: Our analysis found 1862 genes linked to sepsis development, enriched in functions like neutrophil extracellular trap formation (NETs) and complement/coagulation cascades. With disease progression, immune activation-associated cells were inhibited, while immune suppression-associated cells were activated. Next, the drug repositioning method identified candidate drugs, such as alpha-1 antitrypsin, that may play a therapeutic role by targeting neutrophil elastase (NE) to inhibit NETs. Animal experiments proved that alpha-1 antitrypsin treatment can improve the survival rate, reduce sepsis score, reduce the levels of inflammation markers in serum, and alleviate muti-organ morphological damage in mice with sepsis. The further results showed that α-1 antitrypsin can inhibit the NETs by suppressing the NE for the treatment of sepsis. SIGNIFICANCE: Alpha-1 antitrypsin acted on the NE to inhibit NETs thereby protecting mice from sepsis-induced inflammation and coagulation.

Clinical and Analytical Comparison of Monoclonal and Polyclonal Immunoassays for Fecal Pancreatic Elastase.

BACKGROUND: Numerous immunoassays have been commercialized to determine pancreatic elastase (PE) in feces in screening for exocrine pancreatic insufficiency (EPI), but how the different assays compare to one another is controversial, especially in the context that all methods use the same cut-off values for interpreting the results obtained on the presence or absence of EPI or the degree of insufficiency if it is present. Our aim was to analytically verify a new method for determining PE, compare the results with a previous method, and verify the declared cut-off values for interpretation of the results. METHODS: PE in the stool was assayed using a previous monoclonal enzyme-linked immunosorbent assay ("ScheBo ELISA") and a new polyclonal particle-enhanced turbidimetric immunoassay ("Bühlmann PETIA"). The direct method comparison of two immunoassays was performed in 40 samples. Clinical comparisons were conducted against each other for the binary determination of "abnormal/normal" elastase levels and the three-way determination of "severe/moderate/no" EPI in 56 samples. The indirect comparison method used external quality assessment (EQA) data to compare the monoclonal and polyclonal immunoassays for PE, and additionally compare the monoclonal ScheBo ELISA to a monoclonal chemiluminescence immunoassay ("DiaSorin CLIA"). RESULTS: Precision in the series and intra-laboratory precision for Bühlmann PETIA met the manufacturer's specifications for the concentration range of limit/lower values and the range of normal values. The Bühlmann PETIA immunoassay on different analytical platforms yielded comparable results and nearly perfect agreement in the case of three-way classification (kappa = 0.89 with 95%CI from 0.79 to 1.00. ScheBo ELISA tends to generate higher values of pancreatic elastase than the Bühlmann PETIA; agreement between the methods was moderate in the case of binary classification (kappa = 0.43; 95% CI 0.25 to 0.62), and substantial in the case of three-way classification (kappa = 0.62; 95% CI 0.50 to 0.75). EQA data analysis showed a statistically significant difference between ScheBo ELISA and Bühlmann PETIA peer groups (p = 0.031), as well as the DiaSorin CLIA and ScheBo ELISA peer groups (p = 0.010). CONCLUSION: The ScheBo ELISA and Bühlmann PETIA do not appear to be commutable in the analytical and clinical context. Our data address a discordance between different mono- and polyclonal immunoassays for pancreatic elastase and the potential of misclassification using its universal cut-off values in screening suspected patients for exocrine pancreatic insufficiency.

Small AAAs: Recommendations for Rodent Model Research for the Identification of Novel Therapeutics.

CLINICAL PROBLEM: Most abdominal aortic aneurysms (AAAs) are small with low rupture risk (<1%/y) when diagnosed but slowly expand to ≥55 mm and undergo surgical repair. Patients and clinicians require medications to limit AAA growth and rupture, but drugs effective in animal models have not translated to patients. RECOMMENDATIONS FOR INCREASING TRANSLATION FROM MOUSE MODELS: Use models that simulate human AAA tissue pathology, growth patterns, and rupture; focus on the clinically relevant outcomes of growth and rupture; design studies with the rigor required of human clinical trials; monitor AAA growth using reproducible ultrasound; and perform studies in both males and females. SUMMARY OF STRENGTHS AND WEAKNESSES OF MOUSE MODELS: The aortic adventitial elastase oral ß-aminopropionitrile model has many strengths including simulating human AAA pathology and modeling prolonged aneurysm growth. The Ang II (angiotensin II) model performed less well as it better simulates acute aortic syndrome than AAA. The elastase plus TGFß (transforming growth factor-ß) blocking antibody model displays a high rupture rate, making prolonged monitoring of AAA growth not feasible. The elastase perfusion and calcium chloride models both display limited AAA growth.

Evaluation of Salivary Biomarkers and Spirometry for Diagnosing COPD in Non-Smokers and Smokers of Polish Origin.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition with global implications. Accurate and timely diagnosis is critical; however, traditional diagnostic methods (based on spirometry) show limitations, prompting the search for predictive biomarkers and modern diagnostic techniques. This study explored the validation of COPD-related biomarkers (C-reactive protein, procalcitonin, neutrophil elastase, and alpha-1 antitrypsin) in saliva. A diverse cohort, including healthy non-smokers, healthy smokers, and COPD patients of Polish origin, underwent spirometry and marker analysis. The data correlated with clinical factors, revealing noteworthy relations. Firstly, salivary biomarker levels were compared with serum concentrations, demonstrating notable positive or negative correlations, depending on the factor. Further analysis within healthy individuals revealed associations between biomarker levels, spirometry, and clinical characteristics such as age, sex, and BMI. Next, COPD patients exhibited an enhanced concentration of biomarkers compared to healthy groups. Finally, the study introduced a breathing assessment survey, unveiling significant associations between self-perceived breathing and spirometric and tested parameters. Outcomes emphasized the relevance of subjective experiences in COPD research. In conclusion, this research underscored the potential of salivary biomarkers as diagnostic tools for COPD, offering a non-invasive and accessible alternative to traditional methods. The findings paved the way for improved modern diagnostic approaches.

The investigation of the interaction determination between carbendazim and elastase, using both in vitro and in silico methods.

Pesticides, including fungicides, are one of the important groups of environmental toxins that affect human and animal health. Studies have shown that these compounds are considered chemical pollutants. Carbendazim is a systemic fungicide. Unfortunately, excessive use of carbendazim has caused environmental pollution all over the world. In this study, the effect of carbendazim on the enzyme elastase (secreted from the endocrine gland of the pancreas) has been investigated. In a study, the performance and reaction of carbendazim with elastase were investigated using spectroscopic techniques. The stability and structure of elastase enzymes were studied under the influence of carbendazim. The results of fluorescence emission and UV-visible absorption spectrum showed that in the presence of carbendazim, there is an increase in UV-Vis absorption and a decrease in the intensity of the intrinsic fluorescence emission in the protein spectrum. Additionally, a decrease in the thermal stability of elastase was observed in the presence of carbendazim. The stability and structure of elastase enzyme were investigated in the presence of carbendazim. The results revealed that the UV-Vis absorption increased due to the presence of carbendazim, as indicated by the hyperchromic spectrum at 220 and 280 nm peaks. Additionally, the intrinsic fluorescence emission in the protein spectrum decreased with increasing carbendazim concentration at three different temperatures (298, 303, and 313 K). Moreover, the study demonstrated that the TM decreased from 2.59 to 4.58 with the increase of carbendazim, suggesting a decrease in the stability of the elastase structure in response to the elevated carbendazim concentration. According to the results of the research, the interaction between elastase and carbendazim has occurred, and changes have been made in the enzyme under the influence of carbendazim. The formation of the complex between elastase and carbendazim was consistent with the results obtained from molecular simulation and confirmed the thermodynamic data.

A case of BRCA1-mutated giant pancreatic acinar cell carcinoma successfully treated with modified FOLFIRINOX therapy and radical resection.

Pancreatic acinar cell carcinoma (PACC) is a rare type of pancreatic cancer; further, its pathogenesis and treatment strategies remain unclear. We report the case of a 70-year-old man who presented with a chief complaint of abdominal distention. Computed tomography scans revealed a large lobulated mass (tumor diameter: 150 mm) in the pancreatic body tail, which was diagnosed as a PACC through endoscopic ultrasonography fine needle aspiration. The other imaging modalities did not reveal distant metastases, and the tumor was classified as resectable. Neoadjuvant chemotherapy was planned after staging laparoscopy ruled out microscopic distant metastasis. First-line chemotherapy with gemcitabine + nab-paclitaxel failed due to tumor growth and worsening abdominal distention. Evaluation using the BRACAnalysis® device indicated that the patient was positive for BRCA1 mutation. Second-line modified FOLFIRINOX (mFFX) resulted in a marked decrease in elastase 1 levels; moreover, a partial antitumor response was observed, which prompted radical resection. After distal pancreatectomy, the patient has survived for 3.5 years without recurrence. BRCA-mutated pancreatic cancer is more likely to respond to mFFX, including platinum, and BRCA mutations have been reported to be highly prevalent in PACC. It is important to evaluate the presence of BRCA mutations in patients with PACC prior to treatment.

Effect of phenylalanine arginyl ß-naphthylamide on the imipenem resistance, elastase production, and the expression of quorum sensing and virulence factor genes in Pseudomonas aeruginosa clinical isolates.

Pseudomonas aeruginosa is one of the most important nosocomial pathogens that possess the ability to produce multiple antibiotic resistance and virulence factors. Elastase B (LasB) is the major factor implicated in tissue invasion and damage during P. aeruginosa infections, whose synthesis is regulated by the quorum sensing (QS) system. Anti-virulence approach is now considered as potential therapeutic alternative and/or adjuvant to current antibiotics' failure. The aim of this study is primarily to find out the impact of the efflux pump inhibitor (EPI) phenylalanine arginyl ß-naphthylamide (PAßN) on the production of elastase B and the gene expression of lasI quorum sensing and lasB virulence factor in clinical isolates of P. aeruginosa. Five P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Antimicrobial susceptibility of isolates was performed by the disk agar diffusion method. Effect of the PAßN on imipenem susceptibility, bacterial viability, and elastase production was evaluated. The expression of lasB and lasI genes was measured by quantitative real-time PCR in the presence of PAßN. All isolates were identified as multidrug-resistant (MDR) and showed resistance to carbapenem (MIC = 64-256 µg/mL). Susceptibility of isolates to imipenem was highly increased in the presence of efflux inhibitor. PAßN significantly reduced elastase activity in three isolates tested without affecting bacterial growth. In addition, the relative expression of both lasB and lasI genes was diminished in all isolates in the presence of inhibitor. Efflux inhibition by using the EPI PAßN could be a potential target for controlling the P. aeruginosa virulence and pathogenesis. Furthermore, impairment of drug efflux by PAßN indicates its capability to be used as antimicrobial adjuvant that can decrease the resistance and lower the effective doses of current drugs.

Diterpenoids from Acanthopanacis Cortex and their anti-inflammatory activity studies.

Acanthopanacis Cortex (A.-C) with a long history of more than1000 years, has been used to treat rheumatism effectively. Nineteen diterpenoids have been isolated from A.-C, including six new compounds (1-6). Among them, compounds 7, 9-11, 13, and 17 were discovered from A.-C for the first time. The structures of 1-6 were determined by analyzing their NMR data and comparing their experimental and calculated electronic circular dichroism spectra. Moreover, the single-crystal X-ray diffraction data of 1, 2, 8, and 14 were provided. The anti-inflammatory activity of 1-5 and 7-18 on neutrophil elastase, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) has been studied in vitro, and the results showed that 15 had almost no inhibitory effects on COX-1 at 200 µM but a significant activity against COX-2 with an IC50 of 0.73 ± 0.006 µΜ. It indicated that compound 15 can provide valuable information for the design of selective COX-2 inhibitors.

Effect of Neurotropic and Immunotropic Drugs on Leukocyte Elastase Activity In Vitro.

Leukocyte elastase is a marker of inflammation. Previously, a relationship was found between the severity of mental disorders in patients and elastase-like activity of blood plasma. The effect of various neurotropic drugs on leukocyte elastase activity was analyzed in an in vitro experiment. We revealed an inhibitory effect of the benzodiazepine tranquilizers diazepam and bromodihydrochlorophenylbenzodiazepine and immunomodulators aminodihydrophthalazinedione and diclofenac on the plasma elastase-like activity of healthy donors and pure human neutrophil elastase. The antipsychotics chlorpromazine and alimemazine, as well as the nootropic vinpocetine increased elastase-like activity in a dose-dependent manner. The activating effect of chlorpromazine and vinpocetine, but not alimemazine, was reproduced in neutrophil elastase. We hypothesized that these drugs can affect the development of inflammatory reactions in the complex therapy of mental disorders.

Neutrophils disrupt B-1a cell homeostasis by targeting Siglec-G to exacerbate sepsis.

B-1a cells, an innate-like cell population, are crucial for pathogen defense and the regulation of inflammation through their release of natural IgM and IL-10. In sepsis, B-1a cell numbers are decreased in the peritoneal cavity as they robustly migrate to the spleen. Within the spleen, migrating B-1a cells differentiate into plasma cells, leading to alterations in their original phenotype and functionality. We discovered a key player, sialic acid-binding immunoglobulin-like lectin-G (Siglec-G), which is expressed predominantly on B-1a cells and negatively regulates B-1a cell migration to maintain homeostasis. Siglec-G interacts with CXCR4/CXCL12 to modulate B-1a cell migration. Neutrophils aid B-1a cell migration via neutrophil elastase (NE)-mediated Siglec-G cleavage. Human studies revealed increased NE expression in septic patients. We identified an NE cleavage sequence in silico, leading to the discovery of a decoy peptide that protects Siglec-G, preserves peritoneal B-1a cells, reduces inflammation, and enhances sepsis survival. The role of Siglec-G in inhibiting B-1a cell migration to maintain their inherent phenotype and function is compromised by NE in sepsis, offering valuable insights into B-1a cell homeostasis. Employing a small decoy peptide to prevent NE-mediated Siglec-G cleavage has emerged as a promising strategy to sustain peritoneal B-1a cell homeostasis, alleviate inflammation, and ultimately improve outcomes in sepsis patients.

Unveiling the metabolites underlying the skin anti-ageing properties of Cytinus hypocistis (L.) L. through a biochemometric approach.

BACKGROUND: The genus Cytinus, recognised as one of the most enigmatic in the plant kingdom, has garnered attention for its bioactive potential, particularly its skin anti-ageing properties. Despite this recognition, much remains to be accomplished regarding deciphering and isolating its most active compounds. HYPOTHESIS: This study aimed to identify the compounds responsible for C. hypocistis skin anti-ageing potential. METHODS: Using multivariate analysis, a biochemometric approach was applied to identify the discriminant metabolites by integrating extracts' chemical profile (Liquid Chromatography-High-Resolution Mass Spectrometry, LCHRMS) and bioactive properties. The identified bioactive metabolite was structurally elucidated by 1D and 2D Nuclear Magnetic Resonance (NMR). RESULTS: Among the studied bioactivities, the anti-elastase results exhibited a significant variation among the samples from different years. After the biochemometric analysis, the compound 2,3:4,6-bis(hexahydroxydiphenoyl)glucose, with a molecular mass of 784.075 Da, was structurally elucidated as the discriminant feature responsible for the outstanding human neutrophil elastase inhibition. Remarkably, the subfraction containing this compound exhibited a tenfold improvement in neutrophil elastase inhibition efficacy compared to the crude extract; its effectiveness fell within the same range as SPCK, a potent irreversible neutrophil elastase inhibitor. Moreover, this subfraction displayed no cytotoxicity or phototoxicity and excellent efficacy for the tested anti-ageing properties. CONCLUSIONS: Hydrolysable tannins were confirmed as the metabolites behind C. hypocistis skin anti-ageing properties, effectively mitigating critical molecular mechanisms that influence the phenotypically distinct ageing clinical manifestations. Pedunculagin was particularly effective in inhibiting neutrophil elastase, considered one of the most destructive enzymes in skin ageing.

Association of the immediate perioperative dynamics of circulating DNA levels and neutrophil extracellular traps formation in cancer patients.

Objectives: Elevated circulating DNA (cirDNA) concentrations were found to be associated with trauma or tissue damage which suggests involvement of inflammation or cell death in post-operative cirDNA release. We carried out the first prospective, multicenter study of the dynamics of cirDNA and neutrophil extracellular trap (NETs) markers during the perioperative period from 24 h before surgery up to 72 h after curative surgery in cancer patients. Methods: We examined the plasma levels of two NETs protein markers [myeloperoxidase (MPO) and neutrophil elastase (NE)], as well as levels of cirDNA of nuclear (cir-nDNA) and mitochondrial (cir-mtDNA) origin in 29 colon, prostate, and breast cancer patients and in 114 healthy individuals (HI). Results: The synergistic analytical information provided by these markers revealed that: (i) NETs formation contributes to post-surgery conditions; (ii) post-surgery cir-nDNA levels were highly associated with NE and MPO in colon cancer [r = 0.60 (P < 0.001) and r = 0.53 (P < 0.01), respectively], but not in prostate and breast cancer; (iii) each tumor type shows a specific pattern of cir-nDNA and NETs marker dynamics, but overall the pre- and post-surgery median values of cir-nDNA, NE, and MPO were significantly higher in cancer patients than in HI. Conclusion: Taken as a whole, our work reveals the association of NETs formation with the elevated cir-nDNA release during a cancer patient's perioperative period, depending on surgical procedure or cancer type. By contrast, cir-mtDNA is poorly associated with NETs formation in the studied perioperative period, which would appear to indicate a different mechanism of release or suggest mitochondrial dysfunction.

Targeting neutrophil elastase is a promising direction for future cancer treatment.

Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition to participating in the body's inflammatory response, NE also plays an important role in cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), and change the tumor microenvironment (TME) to promote tumor progression. Concurrently, NE promotes systemic treatment resistance by inducing EMT. However, it can also selectively kill cancer cells and attenuate tumor development. Sivelestat is a specific NE inhibitor that can be used in the perioperative period of esophageal cancer patients to reduce the incidence of postoperative complications after esophagectomy. In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Meanwhile, targeting the human antibody domains and fragments of NE is also a new way to treat cancer and inflammation-related diseases. This review provides valuable insights into the role of NE in cancer treatment. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies.

Extraction and In Vitro Skincare Effect Assessment of Polysaccharides Extract from the Roots of Abelmoschus manihot (L.).

Obtaining high-added value compounds from agricultural waste receives increasing attention, as it can both improve resource utilization efficiency and reduce waste generation. In this study, polysaccharides are extracted from the discarded roots of Abelmoschus manihot (L.) by the high-efficiency ultrasound-assisted extraction (UAE). The optimized condition was determined as solid-liquid ratio SL ratio = 1:20, temperature T = 30 °C and time T = 40 min, achieving an extraction yield of 13.41%. Composition analysis revealed that glucose (Glc, 44.65%), rhamnose (Rha, 26.30%), galacturonic acid (GalA, 12.50%) and galactose (Gal, 9.86%) are the major monosaccharides of the extract. The extract showed a low degree of esterification (DE) value of 40.95%, and its Fourier-transform infrared (FT-IR) spectrum exhibited several characteristic peaks of polysaccharides. Inspired by the wide cosmetic applications of polysaccharides, the skincare effect of the extract was evaluated via the moisture retention, total phenolic content (TPC) quantification, 2,2-Diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging activity, anti-hyaluronidase and anti-elastase activity experiments. The extract solutions demonstrated a 48 h moisture retention rate of 10.75%, which is superior to that of commercially available moisturizer hyaluronic acid (HA). Moreover, both the TPC value of 16.16 mg GAE/g (dw) and DPPH-free radical scavenging activity of 89.20% at the concentration of 2 mg/mL indicated the strong anti-oxidant properties of the extract. Furthermore, the anti-hyaluronidase activity and moderate anti-elastase activity were determined as 72.16% and 42.02%, respectively. In general, in vitro skincare effect experiments suggest moisturizing, anti-oxidant, anti-radical and anti-aging activities of the A. manihot root extract, indicating its potential applications in the cosmetic industry.