Erythritol aggravates gut inflammation and anxiety-like behavioral disorders induced by acute dextran sulfate sodium administration in mice.

Erythritol is a widely used sugar substitute in food and beverages with beneficial and detrimental roles in obesity and cardiovascular diseases, respectively; however, its influence on inflammatory bowel disease (IBD) and related behavioral disorders is not well understood. Here, we found that erythritol exacerbated gut inflammation by promoting macrophage infiltration and inducing M1 macrophage polarization, thus increasing gut leakage during colitis triggered by acute dextran sulfate sodium (DSS) treatment. Increased gut permeability can cause neuroinflammation and anxiety-like behavioral disorders. In conclusion, our results revealed a negative role for erythritol in gut inflammation and anxiety-like behavioral disorders induced by erythritol administration in a mouse model of acute colitis, suggesting that erythritol intake control may be necessary for IBD treatment.

Fractal analysis of rat dermal tissue in the different injury states.

Scar formation and chronic ulcers can develop following a skin injury. They are the result of the over- or underproduction of collagen. It is very important to evaluate the quality and quantity of the collagen that is produced during wound healing, especially with respect to its structure, as these factors are very important to a complicated outcome. However, there is no standard way to quantitatively analyse dermal collagen. As prior work characterised some potentially fractal properties of collagen, it was hypothesised that collagen structure could be evaluated with fractal dimension analysis. Small-angle X-ray scattering technology (SAXS) was used to evaluate the dermis of rats exposed to graft harvest, burn, and diabetic pathologic states. It was found that almost all collagen structures could be quantitatively measured with fractal dimension analysis. Further, there were significant differences in the three-dimensional (3-D) structure of normal collagen versus that measured in pathologic tissues. There was a significant difference in the 3-D structure of collagen at different stages of healing. The findings of this work suggest that fractal analysis is a good tool for wound healing analysis, and that quantitative collagen analysis is very useful for assessing the structure of dermal collagen.

Can fractal dimension analysis be used in quantitating collagen structure?

It is well known that collagen tissue, especially the collagen structure, plays an important role in wound healing. However, most research on collagen has been qualitative and morphological, based on sections, and cannot be used for real-time monitoring and clinical prediction. There are no standardized methods of quantitative analysis based on the whole skin sample in three dimensions (3-D). In order to explore a 3-D quantitative analysis, we developed a method that was derived from that of material science and physics, combined with our previous technique, X-ray scattering (SAXS). We hypothesized that the dermis might be analysed by fractal dimensions. To test this hypothesis, we performed the analysis in different pathological conditions, such as scar tissue, different time points after wounding, skin in different degrees of burns and skin in diabetes. The results showed that fractal dimension analysis could detect differences in different locations of the scar tissue, at different time points after wounding, and at a different extent of the severity of skin in diabetes. The research demonstrated that fractal dimension analysis can describe the 3-D structure of the collagen tissue of the skin, which will be beneficial for studying wound healing and finding new clinical treatments.

Exploring nanoscale structure change of dermal tissues suffering injury by small angle X-ray scattering and transmission electron microscopy.

Scar formation and wound non-healing often occur during wound repair after skin injury, which are still unresolved. Clinic indicated that the structure played an important role in the wound repair. Our previous research showed that the wound over-healed (scar formation) when the integrity and continuity of dermal tissues was destroyed by injury. Other evidences showed that wound healing was impaired in diabetes because the underlying alternation in their skin tissues occurred caused by advanced glycation end products (AGES) aggregation. In order to explore the changes of the structure of skin at nanoscale, the small angle X-ray scattering (SAXS), compared with transmission electron microscopy (TEM), was applied to observe the skin in different pathological status. The results showed that there were some regular patterns in the structure of dermal tissue. The patterns were changed by different pathological status, which would result in wound healing disorder. These will be beneficial for clarifying the pathological mechanisms of wound healing.

Correlation analysis of expressions of PTEN and p53 with the value obtained by magnetic resonance spectroscopy and apparent diffusion coefficient in the tumor and the tumor-adjacent area in magnetic resonance imaging for glioblastoma.

PURPOSE: To explore the correlation of the expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) and p53 of glioblastoma multiforme (GBM) with the value obtained by magnetic resonance spectroscopy (MRS) and apparent diffusion coefficient (ADC) in the tumor and the tumor-adjacent area in magnetic resonance imaging (MRI). METHODS: A total of 38 patients were operated for GBM. All the patients had received diffusion-weighted imaging (DWI) and MRS prior to surgery. ADC of water molecules and values of metabolite indexes of MRS, including n-acetyl aspartate (NAA), choline (Cho) and creatine (Cr), were recorded, and the ratios of Cho/NAA, Cho/Cr and NAA/Cr were calculated. Hematoxylin-eosin (H&E) staining was done to examine the morphology of tumor and of tumor-adjacent tissues; immunohistochemistry (IHC) was performed to examine the expressions of PTEN and p53 in the tumor and the tumor-adjacent area. Finally, the correlations of the expressions of PTEN and p53 with ADC, Cho/NAA, Cho/Cr and NAA/Cr of the tumor and the tumor-adjacent area were analyzed. RESULTS: H&E staining showed that GBM tissues had disordered morphology, different sizes of cells, large cell nuclei and significant cell heterogeneity. IHC indicated that the expression level of p53 protein in the tumor was significantly higher than in the tumor-adjacent tissues (p<0.05). The expression level of PTEN protein was high in the tumor-adjacent tissues, but significantly deficient in the tumor. DWI showed that the signal of DWI in the tumor was significantly increased, but ADC was decreased compared with the tumor-adjacent area. MRS indicated that the wave band of Cho in the tumor was significantly increased, NAA was significantly lowered, and Cr section was decreased compared with the tumor-adjacent area, while NAA/Cr in the tumor was significantly decreased compared with the tumoradjacent area (p<0.05). Correlation analysis indicated that PTEN levels in the tumor and the tumor-adjacent area were positively correlated with ADC in the corresponding area, while p53 in the tumor and the tumor-adjacent area was negatively correlated with ADC in the corresponding area. Cho/NAA and Cho/Cr in the tumor were positively correlated with p53 in the tumor, but negatively correlated with PTEN in the tumor. However, NAA/Cr of the tumor was irrelevant to the levels of PTEN and p53. CONCLUSIONS: The test results of DWI and MRS of patients with GBM can accurately reflect the inactivation or mutation of PTEN and p53.

Exploring the dermal "template effect" and its structure.

Scar formation is the problem for clinic surgery. Recent studies showed that the scar formation was closely related to the dermal defect. Three-dimensional (3-d) structures of dermal tissues act as a template to modulate cell functions that are essential the regeneration of skin structure and function. The dermal tissue's integrity and continuity is a prerequisite for repair to take place. Loss of the dermal tissue integrity and continuity due to trauma leads to a lack of the template effect, which may be one important mechanism that hinders the recovery of cell function, resulting in scar formation. These studies give us two questions: what is the three-dimensional (3-d) structure of the dermal tissue? How do the tissues form? Up to now, it is well known that the molecular structure of collagen, the micro-structure of microfibril, however, the mesoscopic structure of dermal tissues is still unclear. Our recently rudimentary studies showed the problem might be resolved by phase-contrast micro-tomography with synchrotron radiation, which is likely to open new avenues for further investigations on wound regeneration and skin tissue engineering.

Phase-contrast microtomography with synchrotron radiation technology: a new noninvasive technique to analyze the three-dimensional structure of dermal tissues.

BACKGROUND: Since the three-dimensional (3-D) structure of dermal tissue has an important role in regulating cell behavior and directing the wound healing process, the characteristic of the 3-D structure of dermal tissue needs to be clarified. OBJECTIVE: To explore the different 3-D structures between normal and scar dermal tissues. MATERIAL AND METHODS: Phase-contrast microtomography with synchrotron radiation technology was applied to detect the 3-D structure of dermal tissues. RESULTS: The normal dermal tissue consists of elliptical structures formed by fiber bundles interwoven in a helical manner. A regular louver-like structure was observed on the fibers. In scar tissue, the fiber bundles were arrayed in parallel, the louver-like structures were disordered. CONCLUSION: The study demonstrates the mesoscopic difference between normal dermal tissue and scar tissue, suggests that the high level of interweaving capability of collagen is compromised/lost when dermal tissue is injured, and provides a basis for future studies.

Behavior of dermal fibroblasts on microdot arrays yields insight into wound healing mechanisms.

The behavior of fibroblasts on patterned substrates was examined in order to elucidate the role of dermal structure in wound healing. Dermal fibroblasts were cultured on micro-patterned silicone elastomer substrates designed to enforce cell adhesion only to fibronectin microdots. The morphology, expression of α-smooth muscle actin (α-SMA), proliferation, apoptotic cells, and soluble collagen production of cells were measured. Cells grown on patterned substrates showed some signs of a scar-fibroblast phenotype such as: elongated pseudopodia, enhanced expression of alpha smooth muscle actin (α-SMA), and increased collagen/pre-collagen, in comparison to unpatterned controls. Cells also showed low proliferation rates and high apoptotic index. The results showed that the microdot arrays, acting as a grid of limited focal adhesion sites, could force cells to adopt constrained morphologies and limited adhesion areas, which affect the cytoskeleton, ultimately leading to expression of a scar-tissue fibroblast phenotype. This study provides insight into the regulatory mechanisms of micro-topology on cell behavior in wound healing.

The effect of suppressing discoidin domain receptor expression on keloid formation and proliferation .

UNLABELLED:  BACKGROUND: Discoidin domain receptors (DDR) with tyrosine kinase activity have been identified as novel receptors for modulating collagen production and organization in scar tissue. The purpose of this study was to explore the effect of blocking discoidin domain receptor 1 (DDR1), signaling of keloid fibroblast cells on the inhibition of keloid formation, and proliferation, by means of gene therapy. METHODS: The expression of DDR1 in keloid tissues was investigated by immunohistology and the expression of DDR1 protein in keloid fibroblasts was examined by Western blot analysis. Keloid dermal fibroblasts were infected in vitro with modified phosphorothioate and liposome-encapsulation DDR1-antisense oligodeoxynucleotide (ASODN). Northern blot was used to analyze gene expression of DDR1 in infected keloid dermal fibroblasts and the effect on type I and type III collagen gene expression. Extracellular matrix production in infected fibroblasts was analyzed by [3H] proline incorporation. RESULTS: In keloid tissues, the expression of DDR1 was observed to be widely and strongly distributed. The expression of DDR1 protein was also highly increased in keloid fibroblasts compared to normal skin fibroblasts. This was markedly downregulated in lipid-encoding DDR1-ASODN infected fibroblasts compared to lipid encoding DDR1-NSODN infected fibroblasts and lipid-infected fibroblasts. Type I and type III collagen gene expression and extracellular matrix production also were downregulated markedly in DDR1 ASODN infected fibroblasts. Moreover, the ratio of type I and type III collagen was significantly improved. CONCLUSION: An intrinsic functional difference exists between normal human dermal and keloid fibroblasts in terms of higher DDR1 gene expression in keloid fibroblasts. The quality and quantity of collagen can be improved by downregulating the expression of DDR1 using ASODN. This intervention is potentially useful in controlling fibrosis and keloid formation in clinical settings. .

Exploring the collagen nanostructure of dermal tissues after injury.

Scar often occurred during wound repair. It was known that there were differences in collagen structure in dermal tissues at millimeter scale and micron scale, however, it was not known whether there were differences in collagen structure in dermal tissues at nanoscale during wound repair. In order to compare the difference at nanoscale, skin samples from patients were selected, the control groups were the normal skin from the same patients. These samples were tested by the small angle X-ray scattering techniques (SAXS) and wide angle X-ray scattering (WAXS) techniques. The transmission electron microscopy (TEM) was used as a comparison. The results showed that there were not only significantly differences between the normal tissue and scar tissue, but also between the center and the margin of the scar tissue at nanoscale by SAXS and WAXS, which was not demonstrated by other studies. These findings demonstrated that the SAXS and WAXS were excellent tools to detect the collagen structure at nanoscale and the orientation of the collagen alignment, which was beneficial for skin tissue engineering and skin regenerative medicine.

Antimitotic drug injections and radiotherapy: a review of the effectiveness of treatment for hypertrophic scars and keloids.

Scars are a common complication of surgery or burn wound management. Scars occur over the body, affecting people of both sexes and all ages. Scar therapy is a constant clinical challenge; antimitotic drugs and radiotherapy are used with varying degrees of success. This article examines the success of both these types of treatment modalities.

Preparation and characterization of yBiGaO(3)-(1-x-y)BiScO(3)-xPbTiO(3) piezoelectric ceramics.

The ternary system of yBiGaO(3)-(1-x-y)BiScO(3)-xPbTiO(3) (BGS-PT) ceramics was prepared by using conventional mixing oxide processing. X-ray diffraction analysis revealed that the BGS-PT ceramics showed the perovskite structure. The Curie temperature (TC) of BGSPT ceramics was found to increase with increasing BiGaO3 content. However, a larger BiGaO3 content led to sharply decreased piezoelectric properties, and the secondary phase was formed in the BGS-PT system. BGS-PT ceramics with x = 0.56, y = 0.19 showed a high Curie temperature T(C) and a large piezoelectric constant d(33) of 501??C and 152 pC/N, respectively. The high T(C) of BGS-PT ceramics with usable piezoelectric properties suggests future high-temperature applications.

MicroRNA-27a directly targets KRAS to inhibit cell proliferation in esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are a type of small non-coding RNA that negatively regulate gene expression levels by binding to the 3'-untranslated region of specific target mRNAs. To investigate the role of miR-27a in esophageal squamous cell carcinoma (ESCC), TargetScan software was used to predict the target gene of miR-27a. Kirsten rat sarcoma viral oncogene homolog (KRAS), which has been implicated as a regulator of cell proliferation, differentiation and transformation, was identified as a potential target gene of miR-27a and, thus, was the focus of the present study. Luciferase activity in cells transfected with miR-27a mimics was 48% lower when compared with that of the miRNA-negative control. Furthermore, expression levels of the K-ras protein were reduced by ≤50% in cells cotransfected with an expression vector containing miR-27a and miR-27a binding sequences, when compared with the control. The expression level of miR-27a was significantly lower in ESCC cell lines and tissues when compared with healthy esophageal epithelial cells and tissues. However, the expression level of the target gene, KRAS was upregulated and ESCC cell proliferation was significantly inhibited following miR-27a mimic or small interfering K-ras transfection. In conclusion, the present study demonstrated that the expression level of miR-27a was low in ESCC and that miR-27a directly targets the KRAS gene, resulting in inhibited cell proliferation in esophageal cancer.

[Fibrosis after damage to fat dome structure of skin of pig].

OBJECTIVE: To observe the fibrosis of skin after damage to the fat dome structure in skin of pig. METHODS: Totally 4 pieces of skin grafts of intermediate thickness in the size of 5 cm × 5 cm were obtained from both sides beside the spine of back in each of the 4 female red Duroc pigs with pedicle on one side with Humby knife performed by burn specialists, who were rich in clinical experience. These skin grafts were assigned as thin dermis group (TD). Pedicled tissue grafts in the size of 5 cm × 5 cm with the thickness of 1.5 mm were obtained within the wounds resulted from former incision with the same method mentioned above, and these tissue grafts were set as fat dome group (FD). The above-mentioned two groups of skin grafts were sutured back in situ immediately after completion of the former procedures. On post surgery day (PSD) 7, 14, and 21, 5 wounds were respectively selected according to the random number table for gross observation of the surgical areas. Tissue samples were obtained from corresponding surgical area deep to the deep fascia after gross observation at above-mentioned time points. Some of the tissue samples were used for observation of distribution of collagen fibers in the regions of operation of both groups of skin grafts with HE staining, and the breadth of fibrosis was measured; some of the tissue samples were used for observation of distribution of type I or III collagen fibers in the regions of incision of both two groups of skin grafts with Sirius red staining. Data were processed with two independent sample t test. RESULTS: A little scab on the edge of wounds was observed on PSD 7; all the wounds were healed on PSD 14; a few hairs were observed growing in the surgical area on PSD 21. HE staining showed that traces of incision were observed in the superficial layer of dermis and at the junction between dermis and fat dome at each time point; profuse hyperplasia of collagen fibers with parallel and orderly arrangement were observed in the region of incision of skin grafts in groups TD and FD at each time point. The breadth of fibrosis of the region of incision of skin grafts was respectively (251 ± 31), (240 ± 3 7), and (342 ± 69) µm in group TD, (239 ± 36), (286 ± 61), and (332 ± 28) µm in group FD on PSD 7, 14, 21, without significantly statistical difference (with t values respectively 0.750, -1.971, and 0.375, P values above 0.05). Sirius red staining showed that large amount of type III collagen fibers and small amount of type I collagen fibers arranging parallelly were present in the region of incision of skin grafts in groups TD and FD at each time point. CONCLUSIONS: Under the circumstances of relatively intact restoration of dermal tissue, no excessive fibrosis was observed after simple incisional injury of fat dome in skin of pig.

Three-dimensional insights into dermal tissue as a cue for cellular behavior.

Scar formation after injury is a big problem, which influences the skin function and esthetic appearances. Recent researchers have hinted many directions, one of which has shown that scar formation is related to the loss of integrity in dermal tissues. The structure of dermal tissue, which contains mostly collagen, is not only crucial for the mechanical stability of skin, but also acts as a dermal template, providing contact guidance for regulating cell behavior and restoring normal structure and function to skin that has been damaged by injury. These findings suggest a series of questions. How does contact guidance regulate cell behavior? What is the three-dimensional (3D) architecture of the dermal tissue? How does the native 3D architecture influence cell behavior in vivo? In this paper, combing our recent research, we will review the recent advances in this field, that is, the phenomenon of contact guidance and explore the possible mechanism behind it.

Visualizing the three-dimensional mesoscopic structure of dermal tissues.

Thorough knowledge of dermal tissue structure in three dimensions is not only a prerequisite for understanding the relationship between cells and their extracellular matrix, but also provides a basis for understanding of wound healing and scar formation for designing the ideal scaffold for skin tissue engineering. Here, we show for the first time the visualization of the three dimensional (3D) structure of dermal tissue by phase-contrast microtomography (µCT) with third-generation synchrotron radiation (SR). Compared with irregular dermal tissue (such as scar tissue), the normal dermal tissues were found to consist of a network of elliptically shaped regions containing a web of fibre bundles. The bundles, composed of fibres, were found to be orientated along specific directions, indicative of helical weaving. A regular array of dentate structure was shown on the fibres. The results showed that phase-contrast µCT with SR had a distinct advantage in accurately viewing the 3D microstructure of dermal tissues.

The change of break modulus drives human fibroblast differentiation in 3D collagen gels.

Extracellular matrix is one of the key environmental factors influencing cell survival and provides signals for cell morphological change, migration, proliferation and differentiation. However, the mechanism through which denatured collagen modulates the biological properties of fibroblasts, is unclear. We investigated the regulation of human fibroblast differentiation in vitro grown in collagen gels with different properties. The break modulus of collagen with denatured collagen and half-load normal collagen was reduced compared with that of normal collagen gel. Fibroblasts cultured in denatured collagen gels showed increased expression of matrix metalloproteinase9 ( MMP-9), tissue inhibitor of metalloproteinase 2 (TIMP2), α-smooth muscle actin (α-SMA), osteoblast cadherin, phosphorylated Myosin phosphatase target subunit1 (p-MYPT1), connective tissue growth factor, type I collagen, type III collagen, α-smooth muscle actin messenger RNA, RhoA, rho-associated protein kinase, and transforming growth factor ß receptors 1 and 2 compared with that in cells cultured in normal collagen gel. But there was no significant difference regarding expression level between denatured collagen gel and half-load normal collagen gel .These findings suggest that the change in break modulus caused by decreasing normal collagen concentration may be the key factor inducing fibroblast differentiation.

A successful rescue of systematic inflammatory response syndrome resulting from severe wound infection.

This article reports a critical case of systematic inflammatory response syndrome (SIRS) due to wound infection. By intensive local wound treatment including debridement, topical negative pressure, and topical antibiotics, SIRS was effectively controlled, vital signs stabilized, and the wound healed in 45 days. This case reflects the close association between wound infection and SIRS while highlighting early diagnosis of local pathology and local treatment.

A rare case of diabetic hand ulcer caused by Streptococcus agalactiae.

This study reports the case of a 71-year-old woman with type 2 diabetes whose paronychia rapidly progressed to the right middle finger and then to the whole dorsal aspect necrosis of the right hand. After admission, the diagnosis of diabetic hand ulcer was established and Streptococcus agalactiae found as the pathogen. The authors controlled glucose, used 3% hydrogen peroxide and sulfadiazine silver in routine dressing, as well as surgical debridement, topical negative pressure, and skin grafting. The wound closed in 32 days after surgery. Diabetic hand ulcer is often developed from a small wound. The wound, if neglected, will expand very quickly and may lead to amputation and even death. So early diagnosis, standardized treatment, and postoperative rehabilitation is very important.

[Advances in research of the mechanism of "covert disorder" in diabetic skin].

The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.