Exploring the efficacy of photodynamic antimicrobial chemotherapy on diabetic foot ulcers in rats.

We investigate the efficacy of photodynamic antimicrobial chemotherapy (PACT) and its combination with an antibiotic in the treatment of diabetic foot ulcers (DFUs) in rats using a novel cationic amino acid porphyrin-based photosensitizer. The research findings demonstrate that the combination of novel cationic photosensitizer-mediated PACT and an antibiotic exhibits significant therapeutic efficacy in treating deep ulcers in a rat model of DFUs. Moreover, the PACT + Antibiotic group displays enhanced angiogenesis, improved tissue maturation, and superior wound healing effect. Micro-computed tomography examination showed that the periosteal reaction was most obvious in the PACT + Antibiotic group. The cortical bone volume ratio (BV/TV), the bone mineral density, and trabecular thickness were significantly higher in the PACT + Antibiotic group than in the model group (p < 0.05). The combination of PACT and antibiotic plays a sensitizing therapeutic role, which provides a new idea for the clinical treatment of DFUs.

Exploring the causal relationship between Takayasu arteritis and inflammatory bowel disease using Mendelian randomization.

Takayasu arteritis (TA) and inflammatory bowel disease (IBD) are two distinct diseases; however, previous studies have reported many cases of IBD-TA coexistence. Additionally, the incidence of IBD in patients with TA is estimated to be significantly higher than the incidence in the general population. Therefore, the two diseases are anticipated to be linked. Mendelian randomization (MR) analysis assesses whether an exposure might causally affect an outcome by using genetic variants inherited randomly at conception, thereby reducing the impact of confounding and reverse causality. The present study aimed to investigate the potential causal relationship between TA and IBD using MR analysis. Two-sample MR analysis, in which TA and IBD were regarded as the exposure and outcome, respectively, was conducted to investigate whether the two diseases are causally related using the R TwoSampleMR package. Summary GWAS data of TA consisted of 516 Turkish cohorts and 462 controls, and 119 patients and 993 controls of European ancestry. Summary data of IBD was from a sub-study of the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) that comprised 31,665 cases and 33,977 controls of European ancestry. Additionally, separate MR analyses stratified by the two major subtypes of IBD, Crohn's disease (CD) and ulcerative colitis (UC), were performed. Various statistical tests, including the intercept of MR-Egger regression, funnel plots, Cochran's Q tests, and leave-one-out sensitivity analyses, were employed to assess the presence of heterogeneity and horizontal pleiotropy among single nucleotide polymorphisms (SNPs). In the primary analysis using the inverse-variance weighted (IVW) method, the risk of developing IBD for a patient with TA compared to a non-TA control increased 1.053 times (Odds Ratio (OR) = 1.053, P = 0.065). The MR-Egger method (OR = 1.025, P = 0.470) yielded results consistent with this null finding. However, both the weighted median method (OR = 1.038, P = 0.002) and the weighted mode method (OR = 1.051, P = 0.009) identified a significant harmful causal effect. The MR outcomes from separate subgroup analyses slightly diverged from those of IBD and TA. Specifically, for CD, three methods indicated that TA is a risk factor: IVW estimated the OR as 1.045 (P = 0.032), MR-Egger as 0.997 (P = 0.957), weighed median as 1.028 (P = 0.021), and weighted mode as 1.031 (P = 0.022), respectively. This study represents one of the initial investigations into the potential causal association between TA and IBD. With three MR methods, including the primary IVW approach, indicating a notable effect on TA on CD, our analysis findings offer some indication that TA could be a contributing risk factor for CD.

Blocking CCR10 Expression Activates m6A Methylation and Alleviates Vascular Endothelial Cell Injury.

BACKGROUND: Cardiovascular disease, one of the most common types of disease in clinical practice today, carries a very high risk of disability and death. This research aims to examine genome-wide changes in injured human dermal microvascular endothelial cells (HDMECs) using the Ribonucleic Acid sequencing (RNA-Seq) technique, and to search for key genes influencing N6-methyladenosine (m6A) methylation, thus gaining new insights into future clinical diagnosis and treatment of cardiovascular diseases (CVDs) and laying a foundation for follow-up research. METHODS: Impaired HDMECs (injury group), established by endotoxin intervention, were analyzed by RNA-Seq for differentially expressed genes (DEGs) relative to normal HDMECs (control group). Then, DEGs that might be associated with m6A methylation were selected for expression blocking to observe m6A methylation alterations. The migration, angiogenesis, and inflammatory response of damaged HDMECs were detected by cell scratch assay, western blotting, and Enzyme-linked Immunosorbent Assay (ELISA) experiments, respectively. RESULTS: In this study, 20 DEGs were screened out from the two groups by RNA-Seq, of which 17 were up-regulated and 3 were down-regulated. The C-C motif chemokine receptor 10 (CCR10) was selected for subsequent analysis. Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) identified elevated CCR10 expression and reduced m6A methylation levels in the injury group (p < 0.05). After blocking CCR10 expression in damaged HDMECs by BI6901 (a CCR10 specific blocker) m6A methylation, cell activity, vascular endothelial growth factor A (VEGFA) and CD31 protein expression, as well as relative length and branches of tube formation were found to be increased compared with the injury group, while the levels of inflammatory factors interleukin-1 (IL-1), interleukin-1 (IL-6) and tumor necrosis factor-α (TNF-α) were decreased (p < 0.05). CONCLUSIONS: Blocking CCR10 expression can activate m6A methylation, promote cell activity, inhibit inflammatory reactions and alleviate HDMEC injury, which may become a breakthrough in future diagnosis and treatment of cardiovascular diseases.

Synthesis and biological evaluation of isatin derivatives containing 1,3,4-thiadiazole as potent a-glucosidase inhibitors.

A series of (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-substituted indolin-2-ones derivatives (3a-3m) were designed and synthesized. All newly synthesized compounds were evaluated for their a-glucosidase inhibitory activity with resveratrol as positive control in vitro. Except for 3i and 3j, all of the compounds showed a potent inhibitory activity against a-glucosidase with IC50 values in the range of 3.12 ± 1.25 to 45.95 ± 1.26 µM and the purity of these compounds was greater than 95%. The IC50 values were being compared to the standard resveratrol (IC50 = 22.00 ± 1.15 µM) and it was found that compounds 3b, 3d-3h were found to be more active than resveratrol. Specifically, (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-(4-chlorobenzyl)indolin-2-one (3d) exhibited the most potent a-glucosidase inhibitory activity with IC50 value of 3.12 ± 1.25 µM. The kinetic analysis revealed that compound (3d) is noncompetitive inhibitor. Structure activity relationship has been established for all compounds. Furthermore, the binding interactions of compound 3d with the active site of a-glucosidase were confirmed through molecular docking. This study has identified a new class of potent a-glucosidase inhibitors for further investigation.

STAT3 operates as a novel transcription factor that regulates NEDD4 in Keloid.

Keloid, marked by excessive deposition of extracellular matrix components, usually occurs after cutaneous trauma. The molecular mechanism involved in the etiology of keloid remains largely unknown in spite of extensive studies presented on the mechanism of Keloid. NEDD4 has come to be recognized as a potential mediator implicated in inflammation and keloid that could chronically develop. Despite this, the working mechanism of NEDD4 involved in keloid remains unclear. In our present report, STAT3 was identified as a novel transcriptional factor that can diametrically regulate the transcription of NEDD4 and the translation that ensues. The regulation by STAT3 over NEDD4 can be abolished as long as the p-STAT3 was inactivated in the presence of Niclosamide, a kind of inhibitors that work specifically on STAT3 signaling pathway. In turn, silencing of NEDD4 was also shown to be able to down-regulate the expression of p-STAT3. No direct protein-protein interactions between STAT3 and NEDD4 can be identified in our setting. The data we provided herein enrich the knowledge regarding the molecular mechanism of NEDD4 involved in the pathogenesis of keloid, defining a new regulatory role for STAT3 in keloid.

Finite frequency range iterative learning fault-tolerant control for discrete time-delay uncertain systems with actuator faults.

The subject area considered is discrete linear time delay systems operating repetitively on a finite time interval with actuator faults, where the system resets at the end of each operation. Regulation of the dynamics is by iterative learning control and performance goals imposed over finite frequency intervals for the case of uncertainty in the dynamic model. To derive the results, the generalized Kalman-Yakubovich-Popov lemma is used. A simulation based case study is also given to demonstrate the applicability of the new results.

The Effects of Adipose Stem Cell-Conditioned Media on Fibrogenesis of Dermal Fibroblasts Stimulated by Transforming Growth Factor-ß1.

Adipose-derived stem cells (ASCs) have been shown to enhance wound healing by human dermal fibroblasts; however, the interactions between ASCs and fibroblasts during injury remain unclear. Fibroblasts were treated with ASC-conditioned medium (ASC-CM) with and without transforming growth factor-ß1 (TGF-ß1) stimulation. Fibroblast proliferation, apoptosis, differentiation and expression of extracellular matrix genes and proteins, type I collagen, and type III collagen were measured. Also, wound-healing effect of ASC-CM was verified with in vivo animal study. ASC-CM inhibited proliferation and enhanced apoptosis of fibroblasts under TGF-ß1 stimulation. Furthermore, 10% ASC-CM inhibited α-smooth muscle actin expression in fibroblasts, whereas 100% ASC-CM increased collagen, especially type III, expression in fibroblasts. ASC-CM was found to contain more basic fibroblast growth factor than hepatocyte growth factor, and 100% ASC-CM increased hepatocyte growth factor gene expression in fibroblasts. These results suggest ASCs affect fibrogenesis by dermal fibroblasts stimulated with TGF-ß1 via paracrine signaling by adipocytokines present in ASC-CM. These results also suggest that higher concentrations of ASC-CM increase collagen production and inhibit fibroblast proliferation to avoid excessive fibrogenesis. We demonstrated that a lower ASC-CM concentration attenuated fibroblast differentiation. Additionally, 100% ASC-CM significantly reduced the wound size in an in vivo wound-healing model. In this study, we provided evidence that ASCs modulate fibrogenesis by fibroblasts via paracrine signaling, suggesting that application of ASCs during wound healing may improve the quality of wound repair.

Improved UV/O3 method for measuring the chemical oxygen demand.

We improved the ultraviolet (UV)/O3-based method for measuring chemical oxygen demand (COD) in water. An on-line COD monitoring device was developed and the UV/O3 method was used to oxidize sample solutions. A model was established by using support vector machines (SVM) algorithm to estimate dissolved oxygen and CO2 in solutions. Based on the measured data by each sensor during the oxidation process and the estimated dissolved oxygen and CO2, the UV/O3-based COD test accuracy was improved. This approach overcomes many problems associated with the conventional COD determination techniques such as long analysis time, consumption of expensive and toxic reagents, and production of secondary toxic waste. The effect of important parameters on the measurement of COD was systematically investigated. The improved method was successfully applied to determine the COD of real samples from environmental water. Compared with the standard dichromate method, our UV/O3-based COD test method is more effective. The assay time of 10-15 min/sample can be readily achieved. A practical detection limit of 0.89 mg/L COD with a linear range of 1-300 mg/L was achieved under the normal conditions.

Status of M1 and M2 type macrophages in keloid.

Macrophages, differentiation from monocytes infiltrated in the wound, have been suggested to be involved and to play an important role in the pathogenesis of wound healing. Nevertheless, no evidence has been established regarding M1 and M2 type macrophages in Keloid. To understand the status of M1 and M2 type macrophages in keloid, immunohistochemistry was performed on 30 cases of Keloid tissues and normal controls, with CD68, typical surface marker for M1 and CD163, well-accepted marker for M2 being immunostained. Meanwhile, the glucocorticoid receptor NR3C1 was also detected. As further confirmation, quantitative real-time PCR was utilized to verify the expression of CD68, CD163 and NR3C1 on mRNA level. It was consistently shown that infiltrated M2 macrophages pronouncedly outnumbered M1 macrophages in the dermis of keloids; and that NR3C1 expression was significantly up-regulated in keloids than that in normal controls. In addition, there was a marked correlation between CD163 and NR3C1 expression. Our results suggest that the number of infiltrated M2 macrophages in the dermis of keloids may be linked to the responsiveness to glucocorticoids in the pathogenesis of keloid.

Laser-induced breakdown spectroscopy application in environmental monitoring of water quality: a review.

Water quality monitoring is a critical part of environmental management and protection, and to be able to qualitatively and quantitatively determine contamination and impurity levels in water is especially important. Compared to the currently available water quality monitoring methods and techniques, laser-induced breakdown spectroscopy (LIBS) has several advantages, including no need for sample pre-preparation, fast and easy operation, and chemical free during the process. Therefore, it is of great importance to understand the fundamentals of aqueous LIBS analysis and effectively apply this technique to environmental monitoring. This article reviews the research conducted on LIBS analysis for liquid samples, and the article content includes LIBS theory, history and applications, quantitative analysis of metallic species in liquids, LIBS signal enhancement methods and data processing, characteristics of plasma generated by laser in water, and the factors affecting accuracy of analysis results. Although there have been many research works focusing on aqueous LIBS analysis, detection limit and stability of this technique still need to be improved to satisfy the requirements of environmental monitoring standard. In addition, determination of nonmetallic species in liquid by LIBS is equally important and needs immediate attention from the community. This comprehensive review will assist the readers to better understand the aqueous LIBS technique and help to identify current research needs for environmental monitoring of water quality.

Stability and Hopf bifurcation for a delayed SLBRS computer virus model.

By incorporating the time delay due to the period that computers use antivirus software to clean the virus into the SLBRS model a delayed SLBRS computer virus model is proposed in this paper. The dynamical behaviors which include local stability and Hopf bifurcation are investigated by regarding the delay as bifurcating parameter. Specially, direction and stability of the Hopf bifurcation are derived by applying the normal form method and center manifold theory. Finally, an illustrative example is also presented to testify our analytical results.

Dynamics of a delayed model for the transmission of malicious objects in computer network.

An SEIQRS model for the transmission of malicious objects in computer network with two delays is investigated in this paper. We show that possible combination of the two delays can affect the stability of the model and make the model bifurcate periodic solutions under some certain conditions. For further investigation, properties of the periodic solutions are studied by using the normal form method and center manifold theory. Finally, some numerical simulations are given to justify the theoretical results.

[Multi-center clinical trial of FLAMIGEL (hydrogel dressing) for the treatment of residual burn wound].

OBJECTIVE: To evaluate the effect of FLAMIGEL (hydrogel dressing) on the repair of residual burn wound. METHODS: Sixty burn patients with residual wounds hospitalized in 6 burn units from November 2011 to May 2012 were enrolled in the multi-center, randomized, and self-control clinical trial. Two residual wounds of each patient were divided into groups T (treated with FLAMIGEL) and C (treated with iodophor gauze) according to the random number table. On post treatment day (PTD) 7 and 14, wound healing rate was calculated, with the number of completely healed wound counted. The degree of pain patient felt during dressing change was evaluated using the visual analogue scale (VAS). The mean numbers of wounds with score equal to zero, more than zero and less than or equal to 3, more than 3 and less than or equal to 6, more than 6 and less than or equal to 10 were recorded respectively. Wound secretion or exudate samples were collected for bacterial culture, and the side effect was observed. Data were processed with repeated measure analysis of variance, t test, chi-square test, and nonparametric rank sum test. RESULTS: Wound healing rate of groups T, C on PTD 7 was respectively (67 ± 24)%, (45 ± 25)%, and it was respectively (92 ± 16)%, (72 ± 23)% on PTD 14. There was statistically significant difference in wound healing rate on PTD 7, 14 between group T and group C (F = 32.388, P < 0.01). Ten wounds in group T and four wounds in group C were healed completely on PTD 7, with no significant difference between them (χ(2) = 0, P > 0.05). Forty-two wounds in group T and seven wounds in group C healed completely on PTD 14, with statistically significant difference between them (χ(2) = 42.254, P < 0.01). Patients in group T felt mild pain during dressing change for 37 wounds, with VAS score higher than zero and lower than or equal to 3. Evident pain was observed in patients of group C during dressing change for 43 wounds, and it scored higher than 3 and less than or equal to 6 by VAS evaluation. There was statistically significant difference in mean number of wounds with different grade of VAS score between group T and group C (Z = -4.638, P < 0.01). Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Baumanii, and Staphylococcus epidermidis were all detected in both groups, but there was no statistical difference between group T and group C (χ(2) = 0.051, P > 0.05). No side effect was observed in either of the two groups during the whole trial. CONCLUSIONS: FLAMIGEL can accelerate the healing of residual burn wounds and obviously relieve painful sensation during dressing change.

[Protective effect of lytic cocktail (inhibition of stress) on lung injury in severe burn rat].

OBJECTIVE: To investigate the protective effect of inhibition of stress (lytic cocktail) on lung injury in severe burn rats at early stage. METHODS: Sprague-Dawley rats inflicted with 30% TBSA full-thickness burn were randomly divided into A group (n = 36, fluid resuscitation with administration of lytic cocktail), B group (n = 36, fluid resuscitation only). Lung function was evaluated by partial pressure of oxygen (PaO2) in arterial blood and histopathologic changes on 3, 5, 7, 10 post burn day (PBD). The levels of malonyldialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-alpha(TNF-alpha) and interferon-gamma (IFN-gamma) in lung tissue were measured at the same time points. RESULTS: The PaO2 level in A group on 3 PBD (12.58 +/- 0.41 kPa) was significantly higher than that in B group (8.86 +/- 0.23 kPa, P < 0.01). Compared with those in B group, the levels of MDA and MPO were significantly decreased in A group at each time point (P < 0.05 or 0.01), the levels of TNF-alpha on 3, 5, 7 PBD (P < 0.05 or 0.01) and IFN-gamma on 5, 7, 14 PBD (P < 0.01) were also decreased in A group. Swollen lung mesenchyme was alleviated, infiltration of inflammatory cell was lessened in A group. CONCLUSION: Lytic cocktail combined with immediate fluid resuscitation can inhibit stess response, downregulate the expression of inflammatory factor, ameliorate lung function in severe burn rat at early stage.

Measurement of internal tissue optical properties at ultraviolet and visible wavelengths: Development and implementation of a fiberoptic-based system.

A novel, multi-wavelength, fiberoptic system was constructed, evaluated and implemented to determine internal tissue optical properties at ultraviolet A (UVA) and visible (VIS) wavelengths. Inverse modeling was performed with a neural network to estimate absorption and reduced scattering coefficients based on spatially-resolved reflectance distributions. The model was calibrated with simulated reflectance datasets generated using a condensed Monte Carlo approach with absorption coefficients up to 85 cm(-1) and reduced scattering coefficients up to 118 cm(-1). After theoretical and experimental evaluations of the system, optical properties of porcine bladder, colon, esophagus, oral mucosa, and liver were measured at 325, 375, 405, 445 and 532 nm. These data provide evidence that as wavelengths decrease into the UVA, the dominant tissue chromophore shifts from hemoglobin to structural proteins such as collagen. This system provides a high level of accuracy over a wide range of optical properties, and should be particularly useful for in situ characterization of highly attenuating biological tissues in the UVA-VIS.

[Influence of stress inhibition on invasive infection in burn wound during early postburn stage in severely burned rats].

OBJECTIVE: To investigate the influence of inhibition of stress on the survival rate, organ dysfunction and (Th)1/Th2 cytokine profiles of the rats with invasive infection in the wound at early postburn stage. METHODS: Sprague-Dawley rats inflicted with 30% TBSA full thickness burn were randomly divided into A (n = 36, with immediate resuscitation), B (n = 36, with immediate resuscitation and lytic cocktail administration). After subeschar injection of 0.1 ml Pseudomonas aeruginosa (10(8) CFU/ml) on 3rd postburn day, the subeschar bacterial quantitative analysis, the survival rate at 96 hours after bacteria injection, the parameters of organ dysfunction and the mRNA expression of IL-2, IL-4, IL-10 and IFN-gamma were determined by corresponding methods. RESULTS: The quantity of subeschar bacteria was larger than 1 x 10(5)/gram in both groups. The survival rate in B group (66.7 +/- 2.6)% was obviously higher than that in A group (33.3 +/- 1.7)%, (P < 0.01). Inflammatory infiltration and pathological changes in the internal organs in B group were alleviated obviously compared with A group. The expression of IL-2 mRNA in B group was significantly lower than that in A group before bacterial inoculation, but increased at 48 and 96 hours after bacterial inoculation, while it was lowered in A group at the same time points (P < 0.05). The expression of IFN-gamma mRNA in A group was significantly lower than that in B group (P < 0.01), while that of IL-4 and IL-10 mRNA in A group was evidently higher than that in B group (P < 0.05 approximately 0.01). CONCLUSION: Inhibition of the stress response during early postburn stage could be beneficial to the prevention of the bacterial invasion due to the changes in Th1/Th2 ratio.