Human neutrophil elastase (HNE) is an enzyme that plays a key role in the body\'s inflammatory response. It has been linked to several diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. As potential treatments for these diseases, HNE inhibitors are of great interest. Metabolites derived from plants, particularly terpenoids such as β-caryophyllene found in black pepper and other plants, and geraniol present in several essential oils, are recognized as significant sources of inhibitors for HNE. Because of their ability to inhibit HNE, terpenoids are considered promising candidates for developing novel therapies to treat inflammatory conditions such as COPD and emphysema. Furthermore, nature can serve as an excellent designer, and it may offer a safer drug candidate for inhibiting HNE production and activity in the future. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were searched to get relevant and up-to-date literature on terpenoids as human neutrophil elastase inhibitors. This review focuses on the isolation, chemical diversity, and inhibition of human neutrophil elastase (HNE) of various terpenoids reported from natural sources up to 2022. A total of 251 compounds from various terpenoids classes have been reported. Further, it also provides a summary of HNE inhibitors and includes a thorough discussion on the structure-activity relationship.

BACKGROUND: The Severe congenital neutropenia (SCN) is a rare genetic disease characterized by a deficiency of mature neutrophils in the bone marrow and peripheral blood disorders. After a BALF ACER examination, the patient was found to have a rareMycobacterium abscess infection.
METHODS: We report a case of SCN withMycobacterium abscess infection caused by ELANE gene mutation. Conventional antiinfection and granulocyte colony-stimulating factor (G-CSF) did not ameliorate patient\'s symptoms. The absolute neutrophil count (ANC) most of the time < 0.50 × 109/L.
METHODS: According to Gene sequencing and other tests, the patient was diagnosed with SCN caused by ELANE gene mutation, severe pneumonia, Mycobacteriosis abscess, nutritional iron deficiency anemia, multiple abscesses of the skin, hypergammaglobuloemia, and thrush.
METHODS: Anti-infection agents, abscess incision and drainage, blood transfusion, G-CSF were treated.
RESULTS: The fever subsided, the cough disappeared, the anemia improved, and the ANC improved (0.69 × 109/L). Currently, the patient has been followed up in the outpatient clinic for 20months, during which time fever, bone pain, gingivitis and thrush occasionally appeared. The ANC fluctuated between 0.20 and 1.27 × 109/L, suggesting the need for a timely hematopoietic stem cell transplant (HSCT).
CONCLUSIONS: ELANE gene-related SCN is rare in children, and the possibility of this disease should be considered in children with recurrent severe bacterial infections and a significant reduction in neutrophils in the peripheral blood shortly after birth. In addition to strengthening nursing care and actively preventing and controlling infection, other rare bacterial infections should be considered in clinical practice.

OBJECTIVE: To assess the potential of measurements of pH, exudate composition and temperature in wounds to predict healing outcomes and to identify the methods that are employed to measure them.
METHODS: A systematic review based on the outcomes of a search strategy of quantitative primary research published in the English language was conducted. Inclusion criteria limited studies to those involving in vivo and human participants with an existing or intentionally provoked wound, defined as \'a break in the epithelial integrity of the skin\', and excluded in vitro and animal studies. Data synthesis and analysis was performed using structured narrative summaries of each included study arranged by concept, pH, exudate composition and temperature. The Evidence Based Literature (EBL) Critical Appraisal Checklist was implemented to appraise the quality of the included studies.
RESULTS: A total of 23 studies, three for pH (mean quality score 54.48%), 12 for exudate composition (mean quality score 46.54%) and eight for temperature (mean quality score 36.66%), were assessed as eligible for inclusion in this review. Findings suggest that reduced pH levels in wounds, from alkaline towards acidic, are associated with improvements in wound condition. Metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase (TIMP), neutrophil elastase (NE) and albumin, in descending order, were the most frequently measured analytes in wounds. MMP-9 emerged as the analyte which offers the most potential as a biomarker of wound healing, with elevated levels observed in acute or non-healing wounds and decreasing levels in wounds progressing in healing. Combined measures of different exudate components, such as MMP/TIMP ratios, also appeared to offer substantial potential to indicate wound healing. Finally, temperature measurements are highest in non-healing, worsening or acute wounds and decrease as wounds progress towards healing. Methods used to measure pH, exudate composition and temperature varied greatly and, despite noting some similarities, the studies often yielded significantly contrasting results. Furthermore, a limitation to the generalisability of the findings was the overall quality scores of the research studies, which appeared suboptimal.
CONCLUSIONS: Despite some promising findings, there was insufficient evidence to confidently recommend the use of any of these measures as predictors of wound healing. pH measurement appeared as the most practical method for use in clinical practice to indicate wound healing outcomes. Further research is required to increase the strength of evidence and develop a greater understanding of wound healing dynamics.

BACKGROUND: The proteolytic activity of neutrophil elastase (NE) not only destroys pathogens but also degrades host matrix tissues by generating a localized protease-antiprotease imbalance. In humans, NE is well known to be involved in various acute and chronic inflammatory diseases, such as chronic obstructive pulmonary disease, emphysema, asthma, acute lung injury, acute respiratory distress syndrome and cystic fibrosis. The regulation of NE activity is thought to represent a promising therapeutic approach, and NE is considered as an important target for the development of novel selective inhibitors to treat these diseases.
METHODS: This article summarizes and analyzes patents on NE inhibitors and their therapeutic potential based on a review of patent applications disclosed between 2010 and 2014.
CONCLUSIONS: According to this review of recent NE inhibitor patents, all of the disclosed inhibitors can be classified into peptide- and non-peptide-based groups. The non-peptide NE inhibitors include heterocyclics, uracil derivatives and deuterium oxide. Among the heterocyclic analogs, derivatives of pyrimidinones, tetrahydropyrrolopyrimidinediones, pyrazinones, benzoxazinones and hypersulfated disaccharides were introduced. The literature has increasingly implicated NE in the pathogenesis of various diseases, of which inflammatory destructive lung diseases remain a major concern. However, only a few agents have been validated for therapeutic use in clinical settings to date.

OBJECTIVE: To evaluate the benefit and safety of sivelestat (a neutrophil elastase inhibitor) administration in patients undergoing esophagectomy.
METHODS: Online databases including PubMed, EMBASE, the Cochrane Library, Web of Knowledge, and Chinese databases (Wanfang database, VIP and CNKI) were searched systematically up to November 2013. Randomized controlled trials and high-quality comparative studies were considered eligible for inclusion. Three reviewers evaluated the methodological quality of the included studies, and Stata 12.0 software was used to analyze the extracted data. The risk ratio (RR) was used to express the effect size of dichotomous outcomes, and mean difference (MD) or standardized mean difference was used to express the effect size of continuous outcomes.
RESULTS: Thirteen studies were included in this systematic review and nine studies were included in the meta-analysis. The duration of mechanical ventilation was significantly decreased in the sivelestat group on postoperative day 5 [I (2) = 76.3%, SMD = -1.41, 95%CI: -2.63-(-0.19)]. Sivelestat greatly lowered the incidence of acute lung injury in patients after surgery (I (2) = 0%, RR = 0.27, 95%CI: 0.08-0.93). However, it did not decrease the incidence of pneumonia, intensive care unit stay or postoperative hospital stay, and did not increase the incidence of complications such as anastomotic leakage, recurrent nerve palsy, wound infection, sepsis and catheter-related fever.
CONCLUSIONS: A neutrophil elastase inhibitor is beneficial in patients undergoing esophagectomy. More high quality, large sample, multi-center and randomized controlled trials are needed to validate this effect.

BACKGROUND: Recently, there have been numerous case reports and series describing patients presenting with cutaneous vasculopathy that has been linked to the levamisole frequently found in cocaine.
OBJECTIVE: The purpose of this study was to review all published case reports and series of patients reported with cutaneous vasculopathic findings of lemavisole induced vasculopathy (LIV) associated with cocaine use.
METHODS: A review of PubMed was performed searching the keywords: levamisole, cocaine, in combination with vasculitis, and vasculopathy. Twenty-two case reports and series were available with sufficient data on reported patients to be included. Four patients from the authors\' clinical experience are included as well.
RESULTS: A number of common clinical and pathological findings are reviewed, including lower extremity (46/55 patients, 84%) and ear involvement (40/55 patients, 73%), and positive anti-neutrophil cytoplasmic antibodies (ANCA) findings (p-ANCA 42/48 patients, 88%; anti human neutrophil elastase 11/11 patients, 100%). Similar numbers of patients were treated with systemic corticosteroids as were treated conservatively; there was comparable improvement on follow up.
CONCLUSIONS: There are a number of clinical and laboratory findings that are commonly found in patients with LIV. There is currently insufficient data to recommend treatment with systemic corticosteroids in patients with this condition.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a relatively common, but under-recognized condition which manifests commonly with liver cirrhosis and emphysema. Specific therapy for lung-affected individuals with AATD is augmentation therapy, which consists of intravenous infusion of purified human plasma-derived alpha-1 antitrypsin (AAT). Augmentation therapy was first approved by the United States Food and Drug Administration (FDA) in 1987 for emphysema associated with severe AATD and today, six augmentation therapy preparations, all of which derive from pooled human plasma, have received FDA approval.
METHODS: This paper reviews augmentation therapy for AATD, including the various available commercial preparations, their processing and biochemical differences, evidence regarding biochemical and clinical efficacy, patterns of clinical use, adverse effect profiles, cost-effectiveness and potential uses in conditions other than emphysema associated with AATD. Novel and emerging strategies for treating AATD are briefly discussed next, including alternative dosing and administration strategies, recombinant preparations, small molecule inhibitors of neutrophil elastase and of AAT polymerization, autophagy-enhancing drugs and gene therapy approaches.
CONCLUSIONS: We conclude with a discussion of our approach to managing patients with AATD and use of augmentation therapy.

Elastase is a protease released by polymorphonuclear neutrophils (PMN) during the inflammatory process. Since 1987, seminal elastase-inhibitor complex (Ela/alpha1-PI) has been proposed as a marker of male silent genital tract inflammation. Measured by immunoassay in seminal plasma, Ela/alpha1-PI at a cut-off level of > or = 230 microg/l, is useful in the detection of genital tract inflammation. The prevalence of increased seminal Ela/alpha1-PI in infertile men is significantly higher than that observed in fertile men. The Ela/alpha1-PI level is positively correlated with other seminal fluid markers of male genital tract inflammation: reduced semen volume, citric acid, fructose, and increased albumin, complement component C3, caeruloplasmin, immunoglobulins IgG and IgA, and cytokines interleukins-8 and -6. A higher seminal Ela/alpha1-PI level is significantly associated with tubal damage in female partners. After antibiotic therapy, a decrease of Ela/alpha1-PI level is observed. The presence of tubal damage in the partner may negatively affect the response to antibiotic treatment. A higher seminal Ela/alpha1-PI is associated with lower percentage of sperm with single-stranded deoxyribonucleic acid (DNA) and better fertilization rate in in vitro fertilization. Besides infertility, the determination of Ela/alpha1-PI is useful to confirm the presence of prostate and other male accessory gland bacterial inflammation. Screening for PMN Ela/alpha1-PI is easy to perform and reproducible and is a reliable quantitative test for diagnosis and prognosis of silent genital tract inflammation of couples. Moreover, sequential determinations allow the follow-up of inflammation during and after therapy.

A 39-year-old Japanese woman had been receiving propylthiouracil for 5 years for hyperthyroidism when she developed myalgia, scleritis, proteinuria, fever, and inflammation of the nose. Examination of a renal biopsy specimen showed focal segmental necrotizing glomerulonephritis. Indirect immunofluorescent staining showed a highly positive perinuclear pattern of anti-neutrophil cytoplasmic antibody (ANCA) in her serum. Enzyme-linked immunosorbent assay (ELISA) of the ANCA showed positivity for anti-proteinase 3, anti-myeloperoxidase, anti-leukocyte elastase, and anti-lactoferrin, but anti-cathepsin G and anti-lysozyme were negative. Because ELISA showed the titer of anti-leukocyte elastase antibody to be markedly elevated, we challenged this data by performing dot blot analysis. The patient\'s serum reacted with the native form, but not with denatured leukocyte elastase. Propylthiouracil-induced vasculitis was suspected. Symptoms abated within 2 weeks and all values of ANCA were reduced after the drug was withdrawn. Vasculitis is a rare side-effect of propylthiouracil therapy. Recently it was reported in association with ANCA. We present the findings of this patient and compare them with those described in 19 published cases of propylthiouracil-induced vasculitis associated with ANCA.