Punicalagin increases follicular activation, development and activity of superoxide dismutase 1, catalase, and glutathione peroxidase 1 in cultured bovine ovarian tissues.

Context The overproduction of reactive oxygen species (ROS) during in vitro culture of ovarian tissues impairs follicular development and survival. Aims To evaluate the effects of punicalagin on the development and survival of primordial follicles, stromal cell and collagen fibres, as well as on the levels of mRNA for nuclear factor erythroid 2-related factor 2 (NRF2 ), superoxide dismutase 1 (SOD1 ), catalase (CAT ), glutathione peroxidase 1 (GPX1 ) and perirredoxin 6 (PRDX6 ), and activity of antioxidant enzymes in cultured bovine ovarian tissues. Methods Bovine ovarian cortical tissues were cultured for 6days in α-MEM+ alone or with 1.0, 10.0, or 100.0µM punicalagin at 38.5°C with 5% CO2 . Follicle morphology and growth, stromal cell density, and collagen fibres were evaluated by classical histology, while the expression of mRNA was evaluated by real-time PCR. The activity of enzymes was analysed by the Bradford method. Key results Punicalagin improved follicle survival and development, reduced mRNA expression for SOD1 and CAT , but did not influence stromal cells or collagen fibres. Punicalagin (10.0µM) increased the levels of thiol and activity of SOD1, CAT , and GPX1 enzymes. Conclusions Punicalagin (10.0µM) promotes follicle survival and development and activates SOD1, CAT , and GPX1 enzymes in bovine ovarian tissues. Implications Punicalagin improves follicle development and survival in cultured ovarian tissues.

The fatty liver index and risk of incident venous thromboembolism: the Tromsø Study.

Background: For the relationship between obesity and venous thromboembolism (VTE), nonalcoholic fatty liver disease (recently termed metabolic dysfunction-associated steatotic liver disease) is of interest given the hepatic role in hemostasis. Objectives: We aimed to assess the association between the fatty liver index (FLI), as a proxy for nonalcoholic fatty liver disease, and VTE risk in a population-based cohort. Methods: Data from the Tromsø 4 (1994-1995) and 6 (2007-2008) surveys were used to calculate the FLI in 9870 participants. All VTEs were recorded up to December 31, 2020. We used Cox regression to estimate hazard ratios for VTE with 95% CIs by FLI groups defined according to clinical cut-offs (<30, 30-59, and ≥60). Because waist circumference and body mass index (BMI) are main determinants for FLI calculation, we assessed the potential contribution of FLI to VTE risk beyond these body fat measures. Results: During a median follow-up of 13.1 years, 507 incident VTEs occurred. Compared with the reference group (FLI < 30), the hazard ratios for VTE were 1.5 (95% CI, 1.1-1.9) and 1.8 (95% CI, 1.4-2.3) for the FLI 30-59 and ≥60 groups, respectively, in models adjusted for age, sex, alcohol intake, educational level, and physical activity. The association of FLI with VTE was no longer observed, with risk estimates close to unity, when participants were stratified by clinical categories of waist circumference and BMI. Conclusion: Higher values of the FLI were associated with a higher VTE risk. This association was explained by waist circumference and BMI, which reflect excessive body fat deposition and are determinants of the FLI.

Ultrasonic characterization of microstructural changes due to static recrystallization and grain growth in Inconel 625 and Inconel 718 superalloys.

In many metallic materials such as Inconel superalloys, the microstructure and grain size play an important role in their mechanical and physical properties and could impact the performance during long-term service at the operational temperature. Therefore, on-site detection of the microstructural transformation (such as recrystallization and grain growth) is of primary importance from a structural integrity point of view. Nondestructive evaluation methods such as the ultrasonic attenuation measurement offer a unique advantage that they can be used to evaluate the microstructure evolution of a component during fabrication or service operation. Nondestructive determination of the grain size could help predict the mechanical behavior of the component. In this study, the measured attenuation coefficient was fitted to a theoretical attenuation model to establish the grain size, which shows a strong quantitative agreement with the grain size determined from Electron Backscatter Diffraction (EBSD) analysis. Furthermore, the EBSD texture results confirmed the existence of a recrystallization temperature region previously established using hardness measurements. This experimental evidence demonstrates that ultrasonic attenuation can predict the grain transformation that could occur during material processing or operational service.

Enhanced low-cost lipopeptide biosurfactant production by Bacillus velezensis from residual glycerin.

Biosurfactants (BSFs) are molecules produced by microorganisms from various carbon sources, with applications in bioremediation and petroleum recovery. However, the production cost limits large-scale applications. This study optimized BSFs production by Bacillus velezensis (strain MO13) using residual glycerin as a substrate. The spherical quadratic central composite design (CCD) model was used to standardize carbon source concentration (30 g/L), temperature (34 °C), pH (7.2), stirring (239 rpm), and aeration (0.775 vvm) in a 5-L bioreactor. Maximum BSFs production reached 1527.6 mg/L of surfactins and 176.88 mg/L of iturins, a threefold increase through optimization. Microbial development, substrate consumption, concentration of BSFs, and surface tension were also evaluated on the bioprocess dynamics. Mass spectrometry Q-TOF-MS identified five surfactin and two iturin isoforms produced by B. velezensis MO13. This study demonstrates significant progress on BSF production using industrial waste as a microbial substrate, surpassing reported concentrations in the literature.

Grazing exclusion-induced changes in soil fungal communities in a highly desertified Brazilian dryland.

Soil desertification poses a critical ecological challenge in arid and semiarid climates worldwide, leading to decreased soil productivity due to the disruption of essential microbial community processes. Fungi, as one of the most important soil microbial communities, play a crucial role in enhancing nutrient and water uptake by plants through mycorrhizal associations. However, the impact of overgrazing-induced desertification on fungal community structure, particularly in the Caatinga biome of semiarid regions, remains unclear. In this study, we assessed the changes in both the total fungal community and the arbuscular mycorrhizal fungal community (AMF) across 1. Natural vegetation (native), 2. Grazing exclusion (20 years) (restored), and 3. affected by overgrazing-induced degradation (degraded) scenarios. Our assessment, conducted during both the dry and rainy seasons in Irauçuba, Ceará, utilized Internal Transcribed Spacer (ITS) gene sequencing via Illumina® platform. Our findings highlighted the significant roles of the AMF families Glomeraceae (∼71% of the total sequences) and Acaulosporaceae (∼14% of the total sequences) as potential key taxa in mitigating climate change within dryland areas. Moreover, we identified the orders Pleosporales (∼35% of the total sequences) and Capnodiales (∼21% of the total sequences) as the most abundant soil fungal communities in the Caatinga biome. The structure of the total fungal community differed when comparing native and restored areas to degraded areas. Total fungal communities from native and restored areas clustered together, suggesting that grazing exclusion has the potential to improve soil properties and recover fungal community structure amid global climate change challenges.

Joint effect of ischemic stroke and obesity on the risk of venous thromboembolism: the Tromsø Study.

Background: Patients with ischemic stroke have increased risk of venous thromboembolism (VTE). Obesity is prevalent in stroke patients and a well-established risk factor for VTE. Whether obesity further increases the VTE risk in patients with stroke remains unclear. Objectives: We investigated the joint effect of ischemic stroke and obesity on the risk of incident VTE in a population-based cohort. Methods: Participants (n = 29,920) were recruited from the fourth to sixth surveys of the Tromsø Study (1994-1995, 2001, and 2007-2008) and followed through 2014. Incident events of ischemic stroke and VTE during follow-up were recorded. Hazard ratios (HRs) of VTE with 95% CIs were estimated according to combined categories of ischemic stroke and obesity (body mass index ≥ 30 kg/m2), with exposure to neither risk factors as reference. Results: During a median follow-up of 19.6 years, 1388 participants experienced ischemic stroke and 807 participants developed VTE. Among those with stroke, 51 developed VTE, yielding an incidence rate of VTE after stroke of 7.2 per 1000 person-years (95% CI, 5.5-9.5). In subjects without stroke, obesity was associated with a 1.8-fold higher VTE risk (HR, 1.76; 95% CI, 1.47-2.11). In nonobese subjects, stroke was associated with a 1.8-fold higher VTE risk (HR, 1.77; 95% CI, 1.27-2.46). Obese subjects with stroke had a 2-fold increased VTE risk (HR, 2.44; 95% CI, 1.37-4.36). Conclusion: The combination of obesity and ischemic stroke did not yield an excess risk of VTE. Our findings suggest that obese subjects with ischemic stroke do not have a more than additive risk of VTE.

High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: the HUNT study.

ABSTRACT: MicroRNA-145 (miR-145) has been reported to downregulate the expression of tissue factor and factor XI in vitro and decrease venous thrombus formation in animal models. However, the association between miR-145 and risk of future venous thromboembolism (VTE) in the general population remains unknown. We investigated the association between plasma levels of miR-145 and risk of future VTE in a case-cohort study. Incident VTE cases (n = 510) and a subcohort (n = 1890) were derived from the third survey of the Trøndelag Health Study (HUNT3), a population-based cohort. The expression levels of miR-145 were measured in plasma samples obtained at baseline. The study population was divided into quartiles based on miR-145 levels in participants in the subcohort, and weighted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma levels of miR-145 were inversely associated with VTE risk. Participants with miR-145 levels in the highest quartile had a 49% lower risk of VTE (HR, 0.51; 95% CI, 0.38-0.68) than those with miR-145 in the lowest quartile in age- and sex-adjusted analysis, and the inverse association was most pronounced for unprovoked VTE (HR, 0.39; 95% CI, 0.25-0.61). Risk estimates remained virtually the same after further adjustment for body mass index, and cancer and arterial cardiovascular disease at baseline. In conclusion, elevated expression levels of miR-145 in plasma were associated with decreased risk of future incident VTE. The protective role of miR-145 against VTE is consistent with previous experimental data and suggests that miR-145 has the potential to be a target for VTE prevention.

The Risk of Incident Venous Thromboembolism Attributed to Overweight and Obesity: The Tromsø Study.

BACKGROUND: Obesity is a well-established risk factor for venous thromboembolism (VTE). However, data on the proportion of incident VTEs attributed to overweight and obesity in the general population are limited. OBJECTIVE: To investigate the population attributable fraction (PAF) of VTE due to overweight and obesity in a population-based cohort with repeated measurements of body mass index (BMI). METHODS: Participants from the fourth to seventh surveys of the Tromsø Study (enrolment: 1994-2016) were followed through 2020, and all incident VTEs were recorded. In total, 36,341 unique participants were included, and BMI measurements were updated for those attending more than one survey. BMI was categorized as <25 kg/m2, 25-30 kg/m2 (overweight), and ≥30 kg/m2 (obesity). Time-varying Cox regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). The PAF was estimated based on age- and sex-adjusted HRs and the prevalence of BMI categories in VTE cases. RESULTS: At baseline, the prevalence of overweight and obesity was 37.9 and 13.8%, respectively. During a median follow-up of 13.9 years, 1,051 VTEs occurred. The age- and sex-adjusted HRs of VTE were 1.40 (95% CI: 1.21-1.61) for overweight and 1.86 (95% CI: 1.58-2.20) for obesity compared with subjects with BMI <25 kg/m2. The PAF of VTE due to overweight and obesity was 24.6% (95% CI: 16.6-32.9), with 12.9% (95% CI: 6.6-19.0) being attributed to overweight and 11.7% (95% CI: 8.5-14.9) to obesity. Similar PAFs were obtained in analyses stratified by sex and VTE subtypes (provoked/unprovoked events, deep vein thrombosis, pulmonary embolism). CONCLUSION: Our findings indicate that almost 25% of all VTE events can be attributed to overweight and obesity in a general population from Norway.

Ubiquitin-specific protease 7 (USP7): an emerging drug target for cancer treatment.

INTRODUCTION: Ubiquitin-specific protease 7 (USP7) also known as herpesvirus-associated ubiquitin-specific protease (HAUSP) is a well-characterized cysteine protease that belongs to the largest subfamily of deubiquitinating enzymes (DUBs). It is involved in multiple signaling pathways, some of them dysregulated in malignant tumors. USP7 inhibition can lead to cell growth arrest and apoptosis through inhibition of tumor promoters and stabilization of tumor suppressors, making it a promising druggable target for cancer therapy. AREAS COVERED: This review covers the structure of USP7, its function in multiple signaling pathways and relevance in cancer, as well as recent advances and future perspectives in the development of USP7 inhibitors for cancer therapy. EXPERT OPINION: Literature reports display the multiple antitumor activities of USP7 inhibitors, both in vitro and in vivo. Nonetheless, none have entered clinical trials so far, highlighting the need to delve into a deeper understanding of USP7 binding sites and the development of more accurate compound screening methods. Despite these challenges, further development of USP7 inhibitors is promising as a valuable new approach for cancer treatment, including the ability to address chemoresistance.

Probing the Interactions of Thiazole Abietane Inhibitors with the Human Serine Hydrolases ABHD16A and ABHD12.

12-Thiazole abietanes are highly selective reversible inhibitors of hABHD16A that could potentially alleviate neuroinflammation. In this study, we used synthetic chemistry, competitive activity-based protein profiling, and computational methodologies to try to establish relevant structural determinants of activity and selectivity of this class of compounds for inhibiting ABHD16A over ABHD12. Five compounds significantly inhibited hABHD16A but also very efficiently discriminated between inhibition of hABHD16A and hABHD12, with compound 35 being the most effective, at 100 µM (55.1 ± 8.7%; p < 0.0001). However, an outstanding switch in the selectivity toward ABHD12 was observed in the presence of a ring A ester, if the C2' position of the thiazole ring possessed a 1-hydroxyethyl group, as in compound 28. Although our data were inconclusive as to whether the observed enzyme inhibition is allosteric or not, we anticipate that the structure-activity relationships presented herein will inspire future drug discovery efforts in this field.

Surgery As a Trigger for Incident Venous Thromboembolism: Results from a Population-Based Case-Crossover Study.

Background Surgery is a major transient risk factor for venous thromboembolism (VTE). However, the impact of major surgery as a VTE trigger has been scarcely investigated using a case-crossover design. Aim To investigate the role of major surgery as a trigger for incident VTE in a population-based case-crossover study while adjusting for other concomitant VTE triggers. Methods We conducted a case-crossover study with 531 cancer-free VTE cases derived from the Tromsø Study cohort. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to major surgery and after adjustment for other VTE triggers. Results Surgery was registered in 85 of the 531 (16.0%) hazard periods and in 38 of the 2,124 (1.8%) control periods, yielding an OR for VTE of 11.40 (95% CI: 7.42-17.51). The OR decreased to 4.10 (95% CI: 2.40-6.94) after adjustment for immobilization and infection and was further attenuated to 3.31 (95% CI: 1.83-5.96) when additionally adjusted for trauma, blood transfusion, and central venous catheter. In a mediation analysis, 51.4% (95% CI: 35.5-79.7%) of the effect of surgery on VTE risk could be mediated through immobilization and infection. Conclusions Major surgery was a trigger for VTE, but the association between surgery and VTE risk was in part explained by other VTE triggers often coexisting with surgery, particularly immobilization and infection.

Hand grip strength in venous thromboembolism: risk of recurrence and mortality.

Background: There is limited information on the relationship between muscle strength and recurrence and mortality after incident venous thromboembolism (VTE). Objectives: To investigate whether weak hand grip strength (HGS) was associated with risk of recurrence and mortality in patients with VTE recruited from the general population. Methods: Participants from the Tromsø Study with a first-time VTE (n = 545) were included, and all VTE recurrences and deaths among the participants were recorded in the period 1994 to 2020. Weak HGS was defined as lowest 25th percentile of the general population, and incidence rates for VTE recurrence and mortality according to weak vs normal (>25th percentile) HGS, with 95% CIs, were estimated. Results: There were 90 recurrences and 350 deaths during a median of 3.7 years of follow-up. The fully adjusted hazard ratio (HR) for overall VTE recurrence for those with weak HGS vs those with normal HGS was 2.02 (95% CI, 1.23-3.30). The corresponding HRs for recurrence were 2.22 (95% CI, 1.18-4.17) in patients with a first deep vein thrombosis and 1.60 (95% CI, 0.72-3.57) in patients with a first pulmonary embolism. The cumulative 1-year survival was 74.9% and 77.8% in those with weak and normal HGS, respectively. For overall mortality after incident VTE, the fully adjusted HR for those with weak HGS was 1.34 (95% CI, 1.04-1.72). Conclusion: Weak HGS was associated with an increased risk of recurrent VTE, and the association appeared to be particularly pronounced after incident deep vein thrombosis. There was a slightly lower survival probability among those with weak HGS than among those with normal HGS.

Combined effect of high factor VIII levels and high mean platelet volume on the risk of future incident venous thromboembolism.

BACKGROUND: High factor VIII (FVIII) levels and large platelets, as reflected by a high mean platelet volume (MPV), are separately associated with increased risk of venous thromboembolism (VTE). Whether the combination of high FVIII levels and large platelets has a supra-additive effect on VTE risk is unknown. OBJECTIVES: We aimed to investigate the joint effect of high FVIII levels and large platelets, as reflected by high MPV, on the risk of future incident VTE. METHODS: A population-based nested case-control study with 365 incident VTE cases and 710 controls was derived from the Tromsø study. FVIII antigen levels and MPV were measured in blood samples drawn at baseline. Odds ratios with 95% CIs were estimated across FVIII tertiles (<85%, 85%-108%, and ≥108%) and within predefined MPV strata (<8.5, 8.5-9.5, and ≥9.5 fL). RESULTS: VTE risk increased linearly across FVIII tertiles (Ptrend < .001) in models adjusted for age, sex, body mass index, and C-reactive protein. In the combined analysis, participants with FVIII levels in the highest tertile and an MPV of ≥9.5 fL (ie, joint exposure) had an odds ratio for VTE of 2.71 (95% CI, 1.44-5.11) compared with those with FVIII levels in the lowest tertile and an MPV of <8.5 fL (reference). In the joint exposure group, 52% (95% CI, 17%-88%) of VTEs were attributable to the biological interaction between FVIII and MPV. CONCLUSION: Our results suggest that large platelets, as reflected by high MPV, might play a role in the mechanism by which high FVIII level increases the risk of incident VTE.

Bothrops atrox venom: Biochemical properties and cellular phenotypes of three highly toxic classes of toxins.

Snake venoms have a complex mixture of compounds that are conserved across species and act synergistically, triggering severe local and systemic effects. Identification of the toxin classes that are most damaging to cell homeostasis would be a powerful approach to focus on the main activities that underpin envenomation. Here, we focus on the venom of Bothrops atrox, snake responsible for most of the accidents in Amazon region of South America. We identified the key cytotoxic toxin fractions from B. atrox venom and mapped their biochemical properties, protein composition and cell damage. Five fractions were obtained by mass exclusion chromatography and contained either a single class of enzymatic activity (i.e., L-amino acid oxidases or Hyaluronidases) or different activities co-distributed in two or more protein fractions (e.g., Metalloproteinases, Serine Proteases, or Phospholipases A2). Only three protein fractions reduced cell viability of primary human cells. Strikingly, such activity is accompanied by disruption of cell attachment to substratum and to neighbouring cells. Such strong perturbation of morphological cell features indicates likely defects in tissue integrity in vivo. Mass spectrometry identified the main classes of toxins that contribute to these phenotypes. We provide here a strategy for the selection of key cytotoxic proteins for targeted investigation of their mechanism of action and potential synergism during snakebite envenomation. Our data highlights putative toxins (or combinations of) that may be the focus of future therapeutic interference.

Pedunculated hepatocellular carcinoma masquerading as a giant GIST: A case report.

INTRODUCTION AND IMPORTANCE: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in Indonesia and is well-known as a silent killer disease due to its mortality rate among males. Furthermore, a pedunculated HCC (P-HCC) is a rare subtype challenging to diagnose when presented as an extrahepatic mass. CASE PRESENTATION: A 61-year-old man was admitted to our hospital due to abdominal pain with a palpable mass in the left upper abdomen after being referred from secondary health care. The laboratory results revealed values within normal ranges, except for reactive anti-HCV and anemia, with no evidence of liver abnormalities. CT scan detected a solid mass with a necrotic center and calcified component in the upper left hemiabdomen originating from the submucosa of the greater curvature of the stomach, which were suggestive of gastrointestinal stromal tumor (GIST). It was approximately 12.9 × 10.9 × 18.6 cm sized, multilobulated, well-defined, and infiltrating the splenic vein. CLINICAL DISCUSSION: We did a laparotomy and resections consist of distal gastrectomy, liver metastasectomy (segment 2-3), distal pancreatectomy, and splenectomy. Our operative findings were still suggestive of neoplasm of the stomach, most likely a GIST. However, our histological examination revealed a moderate-poorly differentiated liver cell carcinoma, confirmed with immunohistochemical analysis. He was discharged on the seventh day after the operation without any complications. CONCLUSION: This case illustrates challenges in diagnosing and treating a rare pedunculated hepatocellular carcinoma.

High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism.

BACKGROUND: C1-inhibitor (C1INH) is a broad-acting serine protease inhibitor with anticoagulant activity. The impact of C1INH plasma levels within the normal physiological range on risk of venous thromboembolism (VTE) is unknown. We assessed the association of plasma C1INH levels and VTE risk and evaluated the impact of C1INH on thrombin and plasmin generation in ex vivo assays. METHODS: A nested case-control study with 405 patients with VTE and 829 age- and sex-matched controls was derived from the Tromsø Study. Odds ratios (ORs) with 95% confidence intervals (95% CI) for VTE were estimated across plasma C1INH quartiles. Genetic regulation of C1INH was explored using quantitative trait loci analysis of whole exome sequencing data. The effect of plasma C1INH levels on coagulation was evaluated ex vivo by calibrated automated thrombography. RESULTS: Individuals with C1INH levels in the highest quartile had a lower risk of VTE (OR 0.68, 95% CI: 0.49-0.96) compared with those with C1INH in the lowest quartile. In subgroup analysis, the corresponding ORs were 0.60 (95% CI: 0.39-0.89) for deep vein thrombosis and 0.85 (95% CI: 0.52-1.38) for pulmonary embolism, respectively. No significant genetic determinants of plasma C1INH levels were identified. Addition of exogenous C1INH to normal human plasma reduced thrombin generation triggered by an activator of the intrinsic coagulation pathway, but not when triggered by an activator of the extrinsic coagulation pathway. CONCLUSIONS: High plasma levels of C1INH were associated with lower risk of VTE, and C1INH inhibited thrombin generation initiated by the intrinsic coagulation pathway ex vivo.

Orchid Micropropagation Using Conventional Semi-Solid and Temporary Immersion Systems: A Review.

Orchids, with their astonishingly stunning flowers, dominate the international floricultural market. They are considered prized assets for commercial applications in pharmaceutical and floricultural industries as they possess high therapeutic properties and superior ornamental values. The alarming depletion of orchid resources due to excessive unregulated commercial collection and mass habitat destruction makes orchid conservation measures an extreme priority. Conventional propagation methods cannot produce adequate number of orchids, which would meet the requirement of these ornamental plants for commercial and conservational purposes. In vitro orchid propagation using semi-solid media offers an outstanding prospect of rapidly producing quality plants on a large scale. However, the semi-solid (SS) system has shortcomings with low multiplication rates and high production costs. Orchid micropropagation using a temporary immersion system (TIS) overcomes the limitations of the SS system by reducing production costs and making scaleup and full automation possible for mass plant production. The current review highlights different aspects of in vitro orchid propagation using SS and TIS and their benefits and drawbacks on rapid plant generation.

Exploring the Antimicrobial and Antitumoral Activities of Naphthoquinone-Grafted Chitosans.

Biopolymers obtained from natural macromolecules are noteworthy among materials presenting high biocompatibility and adequate biodegradability, as is the case of chitosan (CS), making this biopolymeric compound a suitable drug delivery system. Herein, chemically-modified CS were synthetized using 2,3-dichloro-1,4-naphthoquinone (1,4-NQ) and the sodium salt of 1,2-naphthoquinone-4-sulfonic acid (1,2-NQ), producing 1,4-NQ-CS and 1,2-NQ-CS by three different methods, employing an ethanol and water mixture (EtOH:H2O), EtOH:H2O plus triethylamine and dimethylformamide. The highest substitution degree (SD) of 0.12 was achieved using water/ethanol and triethylamine as the base for 1,4-NQ-CS and 0.54 for 1,2-NQ-CS. All synthesized products were characterized by FTIR, elemental analysis, SEM, TGA, DSC, Raman, and solid-state NMR, confirming the CS modification with 1,4-NQ and 1,2-NQ. Chitosan grafting to 1,4-NQ displayed superior antimicrobial activities against Staphylococcus aureus and Staphylococcus epidermidis associated with improved cytotoxicity and efficacy, indicated by high therapeutic indices, ensuring safe application to human tissue. Although 1,4-NQ-CS inhibited the growth of human mammary adenocarcinoma cells (MDA-MB-231), it is accompanied by cytotoxicity and should be considered with caution. The findings reported herein emphasize that 1,4-NQ-grafted CS may be useful in protecting injured tissue against bacteria, commonly found in skin infections, until complete tissue recovery.

Impact of the von Willebrand factor-ADAMTS-13 axis on the risk of future venous thromboembolism.

BACKGROUND: von Willebrand factor (VWF) and its cleaving protease, ADAMTS-13, form a pivotal axis that regulates hemostasis. However, the role of the VWF-ADAMTS-13 axis in the risk of future venous thromboembolism (VTE) is unknown. OBJECTIVES: To investigate whether plasma ADAMTS-13 levels and an imbalance with VWF levels, assessed as the VWF/ADAMTS-13 ratio, are associated with the risk of future VTE. PATIENTS/METHODS: A population-based nested case-control study, comprising 383 incident VTE cases and 780 age- and sex-matched controls, was derived from the Tromsø study cohort (1994-2007). Antigen levels of ADAMTS-13 and VWF were measured in plasma samples obtained at cohort baseline. Odds ratios (ORs) with 95% CIs were estimated according to quartile cutoffs of ADAMTS-13 and VWF/ADAMTS-13 ratio determined in controls. RESULTS: In age- and sex-adjusted analysis, ADAMTS-13 levels were inversely associated with the VTE risk, with an OR of 1.40 (95% CI, 0.99-1.99) for the lowest vs highest quartiles. The VWF/ADAMTS-13 ratio was linearly associated with the VTE risk (P for trend = .001), with an OR of 1.70 (95% CI, 1.19-2.43) for the highest vs lowest quartiles, and the association was particularly pronounced for unprovoked VTE (OR, 2.81; 95% CI, 1.65-4.81). The ORs were only slightly attenuated after additional adjustments for body mass index and C-reactive protein. CONCLUSIONS: Lowered ADAMTS-13 levels and an imbalance between ADAMTS-13 and VWF levels, reflected by an increased VWF/ADAMTS-13 ratio, were associated with an increased risk of future VTE. Our findings suggest that the VWF-ADAMTS-13 axis is involved in the pathogenesis of VTE.