Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Metabolic, behavioural, and psychosocial risk factors and cardiovascular disease in women compared with men in 21 high-income, middle-income, and low-income countries: an analysis of the PURE study.

BACKGROUND: There is a paucity of data on the prevalence of risk factors and their associations with incident cardiovascular disease in women compared with men, especially from low-income and middle-income countries. METHODS: In the Prospective Urban Rural Epidemiological (PURE) study, we enrolled participants from the general population from 21 high-income, middle-income, and low-income countries and followed them up for approximately 10 years. We recorded information on participants' metabolic, behavioural, and psychosocial risk factors. For this analysis, we included participants aged 35-70 years at baseline without a history of cardiovascular disease, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (cardiovascular disease deaths, myocardial infarction, stroke, and heart failure). We report the prevalence of each risk factor in women and men, their hazard ratios (HRs), and population-attributable fractions (PAFs) associated with major cardiovascular disease. The PURE study is registered with ClinicalTrials.gov, NCT03225586. FINDINGS: In this analysis, we included 155 724 participants enrolled and followed-up between Jan 5, 2005, and Sept 13, 2021, (90 934 [58·4%] women and 64 790 [41·6%] men), with a median follow-up of 10·1 years (IQR 8·5-12·0). At study entry, the mean age of women was 49·8 years (SD 9·7) compared with 50·8 years (9·8) in men. As of data cutoff (Sept 13, 2021), 4280 major cardiovascular disease events had occurred in women (age-standardised incidence rate of 5·0 events [95% CI 4·9-5·2] per 1000 person-years) and 4911 in men (8·2 [8·0-8·4] per 1000 person-years). Compared with men, women presented with a more favourable cardiovascular risk profile, especially at younger ages. The HRs for metabolic risk factors were similar in women and men, except for non-HDL cholesterol, for which high non-HDL cholesterol was associated with an HR for major cardiovascular disease of 1·11 (95% CI 1·01-1·21) in women and 1·28 (1·19-1·39) in men, with a consistent pattern for higher risk among men than among women with other lipid markers. Symptoms of depression had a HR of 1·09 (0·98-1·21) in women and 1·42 (1·25-1·60) in men. By contrast, consumption of a diet with a PURE score of 4 or lower (score ranges from 0 to 8), was more strongly associated with major cardiovascular disease in women (1·17 [1·08-1·26]) than in men (1·07 [0·99-1·15]). The total PAFs associated with behavioural and psychosocial risk factors were greater in men (15·7%) than in women (8·4%) predominantly due to the larger contribution of smoking to PAFs in men (ie, 1·3% [95% CI 0·5-2·1] in women vs 10·7% [8·8-12·6] in men). INTERPRETATION: Lipid markers and depression are more strongly associated with the risk of cardiovascular disease in men than in women, whereas diet is more strongly associated with the risk of cardiovascular disease in women than in men. The similar associations of other risk factors with cardiovascular disease in women and men emphasise the importance of a similar strategy for the prevention of cardiovascular disease in men and women. FUNDING: Funding sources are listed at the end of the Article.

Number of standard modifiable risk factors and mortality in patients with first-presentation ST-segment elevation myocardial infarction: insights from China Acute Myocardial Infarction registry.

BACKGROUND: Recent publications reported a paradoxical finding that there was an inverse association between the number of standard modifiable risk factors (SMuRFs; smoking, hypertension, diabetes, and hyperlipidemia) and mortality in patients with myocardial infarction. However, the current evidence is only limited to those highly developed countries with advanced medical management systems. METHODS: The China Acute Myocardial Infarction registry is a prospective observational study including patients with acute myocardial infarction from three-level hospitals across 31 administrative regions throughout mainland China. A total of 16,228 patients with first-presentation ST-elevation myocardial infarction (STEMI) admitted to hospitals from January 2013 to September 2014 were enrolled in the current analysis. Cox proportional hazard models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital treatments were used to assess the association of the number of SMuRFs with all-cause mortality at 30 days after STEMI presentation. RESULTS: A total of 1918 (11.8%), 11,503 (70.9%), and 2807 (17.3%) patients had 0, 1-2, and 3-4 SMuRFs at presentation, respectively. Patients with fewer SMuRFs were older and more likely to be females, experienced longer pre-hospital delays, and were less likely to receive primary percutaneous coronary intervention and evidence-based medications. Compared with those without any SMuRF, patients with 1-2 SMuRFs and 3-4 SMuRFs were associated with an HR of 0.74 (95% CI, 0.63-0.87) and 0.63 (0.51-0.77) for all-cause mortality up to 30 days in the unadjusted model (Ptrend < 0.0001). However, after multivariate adjustment, the number of SMuRFs was positively associated with increased mortality risk (HR for 1-2 SMuRFs, 1.15 [0.95-1.39]; HR for 3-4 SMuRFs, 1.31 [1.02-1.68]; Ptrend = 0.03), and the association was only significant among patients admitted to hospitals beyond 12 h from onset (HR for 1-2 SMuRFs, 1.39 [1.03-1.87]; HR for 3-4 SMuRFs, 2.06 [1.41-3.01]) but not their counterparts (Pinteraction = 0.01). CONCLUSIONS: The increased crude mortality risk among patients without SMuRFs is explained by confounding factors related to their poor risk profiles (old age, longer pre-hospital delays, and poor clinical management). After multivariate adjustment, a higher risk-factor burden was associated with poor prognosis among patients with STEMI.

Modifiable risk factors associated with cardiovascular disease and mortality in China: a PURE substudy.

AIMS: To examine the incidence of cardiovascular disease (CVD) and mortality in China and in key subpopulations, and to estimate the population-level risks attributable to 12 common modifiable risk factors for each outcome. METHODS AND RESULTS: In this prospective cohort of 47 262 middle-aged participants from 115 urban and rural communities in 12 provinces of China, it was examined how CVD incidence and mortality rates varied by sex, by urban-rural area, and by region. In participants without prior CVD, population-attributable fractions (PAFs) for CVD and for death related to 12 common modifiable risk factors were assessed: four metabolic risk factors (hypertension, diabetes, abdominal obesity, and lipids), four behavioural risk factors (tobacco, alcohol, diet quality, and physical activity), education, depression, grip strength, and household air pollution. The mean age of the cohort was 51.1 years. 58.2% were female, 49.2% were from urban areas, and 59.6% were from the eastern region of China. The median follow-up duration was 11.9 years. The CVD was the leading cause of death in China (36%). The rates of CVD and death were 8.35 and 5.33 per 1000 person-years, respectively, with higher rates in men compared with women and in rural compared with urban areas. Death rates were higher in the central and western regions of China compared with the eastern region. The modifiable risk factors studied collectively contributed to 59% of the PAF for CVD and 56% of the PAF for death in China. Metabolic risk factors accounted for the largest proportion of CVD (PAF of 41.7%), and hypertension was the most important risk factor (25.0%), followed by low education (10.2%), high non-high-density lipoprotein cholesterol (7.8%), and abdominal obesity (6.9%). The largest risk factors for death were hypertension (10.8%), low education (10.5%), poor diet (8.3%), tobacco use (7.5%), and household air pollution (6.1%). CONCLUSION: Both CVD and mortality are higher in men compared with women, and in rural compared with urban areas. Large reductions in CVD could potentially be achieved by controlling metabolic risk factors and improving education. Lowering mortality rates will require strategies addressing a broader range of risk factors.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Variations in the association of height with mortality, cardiovascular disease and cancer in low-, middle- and high-income countries.

BACKGROUND: Final adult height is a useful proxy measure of childhood nutrition and disease burden. Tall stature has been previously associated with decreased risk of all-cause mortality, decreased risk of major cardiovascular events and an increased risk of cancer. However, these associations have primarily been derived from people of European and East Asian backgrounds, and there are sparse data from other regions of the world. METHODS: The Prospective Urban-Rural Epidemiology study is a large, longitudinal population study done in 21 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years. Height was measured in a standardized manner, without shoes, to the nearest 0.1 cm. During a median follow-up of 10.1 years (interquartile range 8.3-12.0), we assessed the risk of all-cause mortality, major cardiovascular events and cancer. RESULTS: A total of 154 610 participants, enrolled since January 2003, with known height and vital status, were included in this analysis. Follow-up event data until March 2021 were used; 11 487 (7.4%) participants died, whereas 9291 (6.0%) participants had a major cardiovascular event and 5873 (3.8%) participants had a new diagnosis of cancer. After adjustment, taller individuals had lower hazards of all-cause mortality [hazard ratio (HR) per 10-cm increase in height 0.93, 95% confidence interval (CI) 0.90-0.96] and major cardiovascular events (HR 0.97, 95% CI 0.94-1.00), whereas the hazard of cancer was higher in taller participants (HR 1.23, 95% CI 1.18-1.28). The interaction p-values between height and country-income level for all three outcomes were <0.001, suggesting that the association with height varied by country-income level for these outcomes. In low-income countries, height was inversely associated with all-cause mortality (HR 0.88, 95% CI 0.84-0.92) and major cardiovascular events (HR 0.87, 95% CI 0.82-0.93). There was no association of height with these outcomes in middle- and high-income countries. The respective HRs for cancer in low-, middle- and high-income countries were 1.14 (95% CI 0.99-1.32), 1.12 (95% CI 1.04-1.22) and 1.20 (95% CI 1.14-1.26). CONCLUSIONS: Unlike high- and middle-income countries, tall stature has a strong inverse association with all-cause mortality and major cardiovascular events in low-income countries. Improved childhood physical development and advances in population-wide cardiovascular treatments in high- and middle-income countries may contribute to this gap. From a life-course perspective, we hypothesize that optimizing maternal and child health in low-income countries may improve rates of premature mortality and cardiovascular events in these countries, at a population level.

Therapeutic effect and immune mechanism of chitosan-gentamicin conjugate on Pacific white shrimp (Litopenaeus vannamei) infected with Vibrio parahaemolyticus.

To explore the disease resistance mechanism of chitosan conjugates, chitosan-gentamicin conjugate (CS-GT) was synthesized and systematically characterized, the immune mechanism of CS-GT on Litopenaeus vannamei infected with Vibrio parahaemolyticus was further explored. The results showed that imine groups in CS-GT were effectively reduced. Dietary supplementation of CS-GT can significantly increase the survival rate, total hemocyte counts, the antioxidant and immune related enzyme activity levels of shrimps (P < 0.05), which are all dose-dependent under the experimental conditions. In addition, CS-GT can protect the hepatopancreas from invading bacteria and alleviate inflammation. Particularly, CS-GT promotes the expressions of legumain (LGMN), lysosomal acid lipase (LIPA) and Niemann-Pick type C2 (NPC2) up-regulated. It is speculated that CS-GT may stimulate the lysosome to phagocytose pathogens more effectively. In conclusions, shrimps fed with CS-GT can produce immune response via lysosome and greatly improve the disease resistance to Vibrio parahaemolyticus.

Catechol functionalized chitosan/active peptide microsphere hydrogel for skin wound healing.

Chitosan-based thermosensitive hydrogels have been widely used in drug delivery and tissue engineering, but their poor bioactivity has limited their further applications. Integral active oyster peptide microspheres (OPM) with an average particle diameter of 3.9 µm were prepared with high encapsulation efficiency (72.8%) and loading capacity (11.9%), exhibiting desirable sustained release effects. Using catechol functionalized chitosan (CS-C) as the polymeric matrix, OPM as the filler, and ß-sodium glycerophosphate (ß-GP) as a thermal sensitizer, the thermosensitive hydrogel CS-C/OPM/ß-GP was prepared. Besides, the application of the hydrogel on wound healing was studied, and its biosafety was evaluated. The results of cell migration in vitro showed that the cell migration rate of CS-C/OPM/ß-GP reached 97.47 ± 5.41% within 48 h, indicating that the hydrogel accelerated the migration of L929 cells. As demonstrated in the mouse skin wound experiment, CS-C/OPM/ß-GP hydrogel not only inhibited the aggregation of diversified inflammatory cells and accelerated the generation of collagen fibers and new blood vessels of the wound, but also enhanced the synthesis of total protein (TP) in granulation tissue, and up-regulated the expression of Ki-67 and VEGF in the injury, thereby achieving fast wound healing. Safety evaluation results showed that CS-C/OPM/ß-GP hydrogel was not cytotoxic to L929 cells, and the hemolysis ratio was less than 5% within 1 mg/mL. In conclusion, CS-C/OPM/ß-GP hydrogel is expected as a promising medical dressing for wound healing.

Tea Tree Oil Terpinen-4-ol Protects Gut Barrier Integrity by Upregulation of Tight Junction Proteins via the ERK1/2-Signaling Pathway.

Tea tree oil (TTO) exhibits a potent antioxidant, antibacterial, and anti-inflammatory activity and is commonly used in skincare products. However, it is not clear whether TTO can protect gut barrier damage in inflammatory bowel disease (IBD) patients. Herein, we report the impact of terpinen-4-ol (TER, the primary constituent of TTO), on lipopolysaccharide (LPS)-induced intestinal epithelial cell barrier function impairment in intestinal porcine epithelial cell lines (IPEC-J2) and dextran sulfate sodium (DSS)-induced IBD in mice. TER protected against LPS-induced damage in IPEC-J2 cells in vitro and attenuated DSS-induced colitis in vivo. Added TER promoted the tight junction (TJ) proteins expressing in vitro and in vivo and attenuated the LPS-induced upregulation of ERK phosphorylation in IPEC-J2 cells. However, when an inhibitor of ERK phosphorylation was added, TER did not promote the expression of TJ protein, denoting that the ERK signaling pathway mediates the upregulation of TJ proteins. Our data may propose the potential application of TER in treating IBD.

Marine collagen peptide grafted carboxymethyl chitosan: Optimization preparation and coagulation evaluation.

Uncontrolled bleeding has always been a sudden accident, which is the main cause of casualties in war trauma, emergency events and surgical operations. Rapid hemostatic materials can effectively reduce casualties and save lives. In this paper, marine collagen peptide grafted carboxymethyl chitosan (CMCS-MCP) was synthesized by 1-ethyl-(dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. To obtain CMCS-MCP conjugates with different degrees of substitution (DS), the reaction conditions were investigated by single-factor tests and optimized by response surface methodology. And the sponges of CMCS-MCP were prepared by freeze-thaw cycling and freeze-drying and characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscope (SEM), and X-ray diffraction (XRD). To evaluate the hemostatic properties of CMCS-MCP sponges, in vitro and in vivo hemostasis tests were carried out. The results showed that the optimum preparation conditions were the mass ratio of MCP to CMCS (MMCP/MCMCS) 6:1, reaction temperature 41 °C, and reaction time 16 h. And under which the DS of 58.86% was obtained. Structure analysis showed that MCP had been successfully grafted onto the CMCS molecular chain, and the CMCS-MCP sponges were of high porosity. In vitro and in vivo hemostasis tests showed that the CMCS-MCP sponges had significant procoagulant activities, especially the one with high DS of 58.86%. The hemostasis mechanism may be that the synergistic effects of MCP and CMCS accelerated coagulation through multiple approaches. The CMCS-MCP sponges give a new insight into biomedical hemostasis materials.

Simple risk score based on the China Acute Myocardial Infarction registry for predicting in-hospital mortality among patients with non-ST-segment elevation myocardial infarction: results of a prospective observational cohort study.

OBJECTIVES: To simplify our previous risk score for predicting the in-hospital mortality risk in patients with non-ST-segment elevation myocardial infarction (NSTEMI) by dropping laboratory data. DESIGN: Prospective cohort. SETTING: Multicentre, 108 hospitals across three levels in China. PARTICIPANTS: A total of 5775 patients with NSTEMI enrolled in the China Acute Myocardial Infarction (CAMI) registry. PRIMARY OUTCOME MEASURES: In-hospital mortality. RESULTS: The simplified CAMI-NSTEMI (SCAMI-NSTEMI) score includes the following nine variables: age, body mass index, systolic blood pressure, Killip classification, cardiac arrest, ST-segment depression on ECG, smoking status, previous angina and previous percutaneous coronary intervention. Within both the derivation and validation cohorts, the SCAMI-NSTEMI score showed a good discrimination ability (C-statistics: 0.76 and 0.83, respectively); further, the SCAMI-NSTEMI score had a diagnostic performance superior to that of the Global Registry of Acute Coronary Events risk score (C-statistics: 0.78 and 0.73, respectively; p<0.0001 for comparison). The in-hospital mortality increased significantly across the different risk groups. CONCLUSIONS: The SCAMI-NSTEMI score can serve as a useful tool facilitating rapid risk assessment among a broader spectrum of patients admitted owing to NSTEMI. TRIAL REGISTRATION NUMBER: NCT01874691.

Protective effects of collagen polypeptide from tilapia skin against injuries to the liver and kidneys of mice induced by d-galactose.

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight <3 kDa) in alleviating liver and kidney injuries in aging mice induced by d-galactose (d-gal) and its underlying mechanism of action. First, we characterized TSCP. TSCP was passed through a 3-kDa ultrafiltration membrane, desalted in water by a solid-phase extraction column, purified further by reverse phase-high performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. TSCP contained 17 types of amino acids (AAs) and 41 peptide chains of length 7 AAs to 22 AAs. The content of free AAs and total AAs of TSCP was 13.5% and 93.79%, respectively. Next, we undertook animal experiments. Mice were injected once-daily with D-gal (300 mg/kg body weight, s.c.) for 8 weeks, and TSCP was administered simultaneously once-daily by intragastric gavage. TSCP could visibly improve the decreased body weight, depressed appetite, and mental deterioration of mice triggered by d-gal. TSCP could also alleviate d-gal-induced damage to the liver and kidneys according to histopathology (especially high-dose TSCP). Consistent with these macroscopic and pathologic changes, TSCP could also prevent d-gal-induced increases in serum levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, lipid peroxidation, creatinine and uric acid, as well as decreases in serum levels of immunoglobulin (Ig)G and IgM. Moreover, TSCP improved the activities of superoxide dismutase, catalase, and glutathione peroxidase, but also inhibited the increases in the levels of malondialdehyde and inducible nitric oxide synthase expression in the liver and kidneys of d-gal-treated mice. These results suggest that TSCP can alleviate the injuries to the liver and kidneys in aging mice induced by d-gal, and that its mechanism of action might be, at least partially, associated with attenuation of oxidative stress and enhancement of immune function.

Sponges of Carboxymethyl Chitosan Grafted with Collagen Peptides for Wound Healing.

Burns are physically debilitating and potentially fatal injuries. Two marine biomaterials, carboxymethyl chitosan (CMC) and collagen peptides (COP), have emerged as promising burn dressings. In this paper, sponges of carboxymethyl chitosan grafted with collagen peptide (CMC-COP) were prepared by covalent coupling and freeze drying. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were then used to characterize the prepared sponges. To evaluate the wound healing activity of the CMC-COP sponges, in vitro tests including cell viability scratch wound healing and scald wound healing experiments were performed in rabbits. Appearance studies revealed the porous nature of sponges and FTIR spectroscopy demonstrated the successful incorporation of COP into CMC. The in vitro scratch assay showed that treatment with CMC-COP sponges (at 100 µg/mL) had significant effects on scratch closure. For burn wounds treated with CMC-COP, regeneration of the epidermis and collagen fiber deposition was observed on day 7, with complete healing of the epidermis and wound on days 14 and 21, respectively. Based on the pathological examination by hematoxylin and eosinstaining, the CMC-COP group demonstrated pronounced wound healing efficiencies. These results confirmed that the CMC-COP treatment enhanced cell migration and promoted skin regeneration, thereby highlighting the potential application of these sponges in burn care.

Mussel-Inspired Catechol-Functionalized Hydrogels and Their Medical Applications.

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.

Construction of a composite sponge containing tilapia peptides and chitosan with improved hemostatic performance.

Despite superior hemostasis and repair function, tilapia peptide's application as wounding dressing is greatly limited due to its poor biostability. To expand its application in wounding dressing area, chitosan (CS), with antibacterial activity, biocompatibility and biodegradability, was used to encapsulate tilapia peptides using ionic crosslink method. The results show 10.6w% (loading capacity) of the tilapia peptides are homogenously dispersed in surface or interior of the as-fabricated chitosan/tilapia peptides microspheres (CS/TPM), which leads to greatly improved biostability. In addition, a new composite sponge using CS/TPM as fillers and CS as matrix was then constructed (S-CS/TPM) and used for hemorrhage control. The results indicate that S-CS/TPM can absorb large volume of water, accelerate blood clotting, increase platelet adhesion and promote conversion of fibrinogen to fibrin. Compared with the CS andCS/TPM, the hemostatic efficiency of S-CS/TPM in New Zealand rabbit ear and femoral artery models is much higher. Particularly, the bleeding time was shortened greatly, and the bleeding volume was reduced significantly. In conclusions, our results suggested that S-CS/TPM is a promising hemostatic adjuvant.

Chitosan oligosaccharide-mediated attenuation of LPS-induced inflammation in IPEC-J2 cells is related to the TLR4/NF-κB signaling pathway.

The protective mechanism of chitosan oligosaccharide (COS) against lipopolysaccharides (LPS) -induced inflammatory responses in IPEC-J2 and in mice with DSS dextran sulfate sodium (DSS) -induced colitis is reported. Upon exposure to LPS, the proliferation rate of IPEC-J2 cells markedly decreased, and epithelial cell integrity was compromised. However, COS pretreatment significantly reduced these changes. Low-concentration (200 µg/mL) COS up-regulated Toll-like receptor 4 (TLR4) and nuclear p65 expression, but inhibited LPS-induced expression of nuclear p65, IL-6, and IL-8. Addition of the TLR4 inhibitor reduced nuclear p65, IL-6, and IL-8 expression in IPEC-J2 cells exposed to COS or LPS alone, and a slight up-regulation in nuclear p65 was observed in COS and LPS co-treated cells. Medium-dose COS (600 mg/kg/d) protected against DSS-induced colitis, in which TLR4 and nuclear p65 expression levels were decreased. We postulate that the prevention of both LPS- and DSS -induced inflammatory responses in IPEC-J2 cells and mice by COS are related to the inhibition of the TLR4/NF-κB signaling pathway.

Self-assembled amphiphilic chitosan nanomicelles to enhance the solubility of quercetin for efficient delivery.

Quercetin (QCT) has important functions such as antioxidant, anti-inflammatory and anticancer. However, its applications in food and in drug are restricted owing to its poor water solubility. In this work, a novel amphiphilic wall-material chitosan was synthesized via grafting of chitosan with deoxycholic acid (DA) as hydrophobic group and modified N-acetyl-L-cysteine (NAC) as hydrophilic group. Amphiphilic chitosan was self-assembled to load QCT as nanomicelles by a low-cost and inorganic solvent procedure. Both the encapsulation efficiencies (EE) and drug-loading rates (DL) increased when increasing the grafting rate of DA. There was a bursting release of QCT for the QCT-loaded nanomicelles (CS-DA-NAC-QNMs) from 0 to 8 h, and then the release rate decreased gradually. After releasing for 72 h, the final cumulative release percentages were more than 40%. All the QCT-loaded nanomicelles samples showed good hemocompatibility, and their water solubility and biocompatibility increased evidently. What's more, they exhibited an obvious inhibition rate of A549 cells.

Chitosan hydrogel in combination with marine peptides from tilapia for burns healing.

The purpose of this study was to develop a promising burns dressing. Chiosan (CS) has been widely used as biomaterials, in combination with marine peptides (MPs) extracted from seawater cultured Tilapia, the newly developed material Chitosan-Marine Peptides hydrogels (CSMP) in this study showed antibacterial activity, pro-cell proliferation and migration, well burning healing. Pathological examinations by HE staining demonstrated that CSMP had pronounced wound healing efficiencies. In burn wounds treated with CSMP, reepithelialization and collagen fiber deposition were observed on day 7, the epithelium was completely regenerated by day 14, and the wounds were completely healed by day 21. Furthermore, CSMP can up-regulate the expression of FGF2 and VEGF. Collectively, these results suggest that CSMP may enhance cell migration and promote the skin regeneration, which demonstrates the potential application of CSMP in burning healing.

Marine Collagen Peptides from the Skin of Nile Tilapia (Oreochromis niloticus): Characterization and Wound Healing Evaluation.

Burns can cause tremendous economic problems associated with irreparable harm to patients and their families. To characterize marine collagen peptides (MCPs) from the skin of Nile tilapia (Oreochromis niloticus), molecular weight distribution and amino acid composition of MCPs were determined, and Fourier transform infrared spectroscopy (FTIR) was used to analyze the chemical structure. Meanwhile, to evaluate the wound healing activity, in vitro and in vivo experiments were carried out. The results showed that MCPs prepared from the skin of Nile tilapia by composite enzymatic hydrolysis were composed of polypeptides with different molecular weights and the contents of polypeptides with molecular weights of less than 5 kDa accounted for 99.14%. From the amino acid composition, the majority of residues, accounting for over 58% of the total residues in MCPs, were hydrophilic. FTIR indicated that the main molecular conformations inside MCPs were random coil. In vitro scratch assay showed that there were significant effects on the scratch closure by the treatment of MCPs with the concentration of 50.0 µg/mL. In the experiments of deep partial-thickness scald wound in rabbits, MCPs could enhance the process of wound healing. Therefore, MCPs from the skin of Nile tilapia (O. niloticus) have promising applications in wound care.

Microencapsulation of coupled folate and chitosan nanoparticles for targeted delivery of combination drugs to colon.

Folate-chitosan nanoparticles, co-loaded with 5-fluourouacil (5-FU) and leucovorin (LV) and prepared by ionic gelation technology were physically microencapsulated by enteric polymer using a solvent evaporation method. Average particle size of the microencapsulated particles was in the range of 15 to 35 µm. High drug encapsulation efficiency was obtained for both 5-FU and LV in the microencapsulated particles. Both drugs were in amorphous state in the microencapsulated particles. By enteric coating, excellent pH-dependent release profile was achieved and no drug release was observed in simulated gastric and intestinal fluids. However, when the pH value reached the soluble threshold of Eudragit S-100, a constant and slow drug release was observed. The results indicated that these microencapsulated particles are a promising vehicle for selectively targeting drugs to colon in the chemotherapy of colon cancer.