EDIL3 and VEGF Synergistically Affect Angiogenesis in Endothelial Cells.

Background: Angiogenesis is one of the histologically predominant characteristics of psoriasis. Vascular endothelial growth factor (VEGF) and epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) have critical effects on angiogenesis. Both these proteins are vital proangiogenic factors in tumor occurrence and progression; however, the relationship between EDIL3 and VEGF with psoriasis remains unclear. Objective: We aimed to elucidate the role of EDIL3 and VEGF and the involved mechanisms in psoriasis-associated angiogenesis. Methods: EDIL3 and VEGF expression in cutaneous tissue was determined by immunohistochemical assay. The effects of EDIL3 on VEGF, VEGFR2, and the growth, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were analyzed by Western blotting assay, cell counting kit-8 assay, Transwell assay, and Matrigel tube formation assay. Results: EDIL3 and VEGF levels in psoriatic lesions significantly increased as compared to those in normal individuals and showed a positive relationship with the Psoriasis Area and Severity Index. The downregulation of EDIL3 decreased VEGF and VEGFR2 expression in HUVECs. Moreover, the decreased expression of EDIL3 and VEGF reduced the growth, invasion, and tube formation abilities of HUVECs, while EDIL3 resistance to VEGF and VEGFR2 was restored by using the EDIL3 recombinant protein. Conclusion: These results suggest that psoriasis is also characterized by EDIL3 and VEGF-mediated angiogenesis. Thus, EDIL3 and VEGF could serve as novel targets for treating psoriasis.

Evaluation of 30% supramolecular salicylic acid followed by 1565-nm non-ablative fractional laser on facial acne and subsequent enlarged pores.

The treatment of acne vulgaris and enlarged pore remains challenging. The 30% supramolecular salicylic acid (SSA) is a newly developed form of SA which affects pathogenic factors of acne. Non-ablative fractional laser (NAFL) promotes remodeling and decreases sebum excretion with minimal side effect. The current study was aimed to evaluate the sequential modality with 30% SSA followed by 1565-nm NAFL on facial acne and subsequent enlarged pores. A 20-week-duration prospective study was performed. Consecutive 4 sessions of 30% SSA treatment were conducted, at 2-week intervals. Two weeks after the last session of 30% SSA, 3 sessions of 1565-nm NAFL treatment were applied, at 4-week intervals. The noninvasive devices measured scores of red areas and pores, cuticle moisture, and sebum secretion. The main subjective evaluation was global acne grading system (GAGS). The side effects were recorded. Compared to baseline, the scores of red areas and pores, sebum secretion, and GAGS significantly decreased after series sessions of 30% SSA treatments (P < 0.05). The sequential application of 1565-nm NAFL maintained the good results (P < 0.05, comparing to baseline) and even further decreased the sebum secretion (P < 0.05, comparing to SSA). The cuticle moisture remained unchanged during whole period, and side effects including tingling sensation, pain, erythema, and edema were quickly reversible and acceptable. The significant improvements of acne and pores were produced by 30% SSA, and 1565-nm NAFL inhibited the sebum secretion and maintained the efficacies of 30% SSA. The sequential modality of 30% SSA followed by 1565-nm NAFL was an alternative choice for acne vulgaris companied with enlarged pores.

Dietary supplementation for female infertility: Recent advances in the nutritional therapy for premature ovarian insufficiency.

Premature ovarian insufficiency (POI) ranks top in the reproductive disorders that may impair multiple functioning systems, reduce the quality of life and ultimately deprive patients of their fertility among women. Symptoms can be partially alleviated by present hormone replacement therapy that cannot improve conception or decrease occurrence rates of systemic complication. Nutritional dietary supplements are attracting more and more attention because of their safety, bioavailability, and efficacy for well-being. Nutrients in the daily food are composed of carbohydrates, fat and lipoprotein, protein and polypeptide, vitamins, and vegetable or fruits containing phytoestrogens. These are functional nutrients due to the proliferative, anti-inflammatory, anti-oxidant, and mitochondria-protective potential during the course of menopause. Apart from dietary nutrients, microbe-related nutritional substances, including probiotics, prebiotics and the combination-synbiotics, display high potential as well in supporting estrous cycle, ovarian viability and modulating other vital reproductive functions. The present review will discuss dietary and microbial nutrients and their roles and applications in the living body based upon animal or human research, evaluate possible effect mechanisms from molecular, cellular and tissue levels, and provide insights into nutritional therapy for prolonging reproductive lifespan in female patients.

EDIL3 influenced the αvß3-FAK/MEK/ERK axis of endothelial cells in psoriasis.

One of the earliest events in the development of psoriatic lesion is a vascular network expansion. The abnormal vascular network is associated with increased endothelial cells (ECs) survival, proliferation, adhesion, migration, angiogenesis and permeability in psoriatic lesion. Our previous study demonstrated that epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) derived from psoriatic dermal mesenchymal stem cells (DMSCs) promoted cell-cell adhesion, migration and angiogenesis of ECs, but the molecular mechanism of upstream or downstream has not been explored. So, this study aimed to explore the association between EDIL3 derived from DMSCs (DMSCs-derived EDIL3) and psoriasis-associated angiogenesis. We injected recombinant EDIL3 protein to mouse model of psoriasis to confirm the roles of EDIL3 in psoriasis. Besides, we employed both short-interference RNA (si-RNA) and lentiviral vectors to explore the molecular mechanism of EDIL3 promoting angiogenesis in psoriasis. In vivo, this research found that after injected recombination EDIL3 protein, the epidermis thickness and microvessel density were both elevated. EDIL3 accelerated the process of psoriasis in the IMQ-induced psoriasis-like mouse model. Additionally, we confirmed that in vitro DMSCs-derived EDIL3 is involved in the tube formation of ECs via αvß3-FAK/MEK/ERK signal pathway. This suggested that DMSCs-derived EDIL3 and αvß3-FAK/MEK/ERK signal pathway in ECs play an important role in the pathogenesis of psoriasis. And the modification of DMSCs, EDIL3 and αvß3-FAK/MEK/ERK signal pathway will provide a valuable therapeutic target to control the angiogenesis in psoriasis.

Del-1 in Psoriasis Induced the Expression of αvß3 and α5ß1 in Endothelial Cells.

OBJECTIVE: Psoriasis is a chronic inflammatory skin disease highly depending on angiogenesis. Our prior results showed that the mRNA and protein of Del-1 in dermal mesenchymal stem cells (dMSCs) was up-regulated from psoriasis. Our aim was further to investigate the role of Del-1 from dMSCs in the pathogenesis of psoriasis and confirm the effect of Del-1 on the pathogenesis of psoriasis. METHODS: We conducted an immunohistochemistry experiment to further investigate the expression of Del-1in psoriatic lesions. In addition, dMSCs with over-expressed Del-1 via the lentiviral vector of Del-1 were co-cultured with ECs, and the protein expression of integrins (αvß3, αvß5 ,and α5ß1) of ECs were detected by western blotting. RESULTS: This research showed that Del-1 was significantly increased in lesions of patients with psoriasis (p< .05, 9.96 vs. 2.18), and Del-1 from dMSCs successfully induced up-regulation of integrins α5ß1 and αvß3 (all p < .05). CONCLUSION: This study demonstrated that Del-1 from dMSCs was involved in the pathogenesis of psoriasis through induced angiogenesis. And Del-1, αvß3 and α5ß1 may be potential new targets for inhibiting angiogenesis in psoriasis.

Androgen-induced gut dysbiosis disrupts glucolipid metabolism and endocrinal functions in polycystic ovary syndrome.

BACKGROUND: The characteristics of polycystic ovary syndrome (PCOS), a common reproductive endocrinal disorder, are high incidence, complicated aetiology and poor therapeutic effects. PCOS patients frequently exhibit gut dysbiosis; however, its roles in the regulation of metabolic and endocrinal balances in PCOS pathophysiology are not clear. RESULTS: In this study, gut dysbiosis was reproduced in dehydroepiandrosterone (DHEA)-induced PCOS-like rats. An antibiotic cocktail was used to eliminate gut microbiota during DHEA treatment; however, depletion of the gut microbiota did not prevent the occurrence of PCOS phenotypes in DHEA-treated rats. DHEA-shaped gut microbiota transplanted to pseudo germ-free recipients trigged disturbances in hepatic glucolipid metabolism and reproductive hormone imbalance. The clinical features of PCOS may be correlated with the relative abundance of gut microbes and the levels of faecal metabolites in faecal microbiota transplantation (FMT) recipient rats. CONCLUSION: These findings indicate that androgen-induced gut microbiota dysbiosis may aggravate metabolic and endocrinal malfunction in PCOS. Video Abstract.

Dermal mesenchymal stem cells promoted adhesion and migration of endothelial cells by integrin in psoriasis.

The unusual dilatation of dermal capillaries and angiogenesis played important roles in psoriasis. Some genes and proteins of dermal mesenchymal stem cells (DMSCs) from psoriasis are abnormal and related to the function of endothelial cells (ECs). The present study was aimed to evaluate whether psoriatic DMSCs could affect adhesion and migration of ECs through neovascularization-related integrins in psoriasis. Human DMSCs, collected from psoriasis lesions and healthy skin, respectively, were cocultured with human umbilical vein endothelial cells (HUVECs). The expression levels of three integrins, that is, αvß3, αvß5, and α5ß1 in HUVECs were tested by quantitative real-time polymerase chain reaction and Western blot analysis. The adhesion and migration of HUVECs were detected by adhesion assay and migration assay. The results showed that in psoriasis group, the expression of αVß3 and α5ß1 of HUVECs markedly increased 2.50- and 3.71-fold in messenger RNA levels, and significantly increased 1.63- and 1.92-fold in protein levels, comparing to healthy control group (all p < .05). But ß5 was not significantly different between the two groups (p > .05). In addition, compared with control, psoriatic DMSCs promoted HUVECs adhesion by 1.62-fold and migration by 2.91-fold (all p < .05). In conclusion, psoriatic DMSCs impact HUVECs adhesion and migration by upregulating the expression of integrins αVß3 and α5ß1.

Psoriasis-associated angiogenesis is mediated by EDIL3.

The dermal mesenchymal stem cells (DMSCs) from psoriasis display higher expression level of epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3), while EDIL3 can bind integrins, including αvß3 and αvß5, to regulate angiogenesis. To assess the role of EDIL3 derived from DMSCs of psoriasis (P-DMSCs) in angiogenesis, in vitro, EDIL3 of DMSCs from psoriasis was silenced by interfering EDIL3. Then the efficacy of silencing EDIL3 was tested by fluorescent flag, qRT-PCR and western blotting. And, in vitro, the relationship of EDIL3 in DMSCs with the angiogenesis of HUVECs were investigated through co-culture system. In vivo, EDIL3 recombinant protein was injected into IMQ cream-induced psoriasis-like skin lesions of mouse and EDIL3-associated tube formation were determined using Image J software. Our results showed the capacity of the adhesion, migration and tube formation of HUVECs in all psoriatic DMSCs groups were significantly higher compared with the control and si-EDIL3 groups (all P<0.05) in vitro. Moreover, under stimulated by EDIL3 recombinant protein, EDIL3-associated tube formation was dramatically elevated in vivo (P<0.01). In this study, EDIL3 could promote the adhesion, migration and tube formation of ECs and participant in the angiogenesis pathogenesis of psoriasis through affecting biological function on ECs both in vitro and in vivo. The results suggest a potential role of the critical pro-angiogenic factor EDIL3 in psoriasis therapy.

Changes in the vaginal microbiota associated with primary ovarian failure.

BACKGROUND: Primary ovarian failure (POF) is defined as follicular failure in women of reproductive age. Although many factors are speculated to contribute to the occurrence of POF, the exact aetiology remains unclear. Moreover, alterations in the microbiome of patients with POF are poorly studied. RESULTS: This study investigated the vaginal microbiota of 22 patients with POF and 29 healthy individuals. High-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to evaluate the relationships between the vaginal flora and clinical characteristics of POF. Different from results of previous studies, we found that the diversity and richness of the vaginal flora of patients with POF was significantly different from those of healthy controls. Comparison of the vaginal flora of patients with POF with that of menopausal women revealed that the relative abundance of Lactobacillus was significantly reduced in the latter. A reduced abundance of Lactobacillus was furthermore associated with a lower pregnancy success rate. Of particular interest is that L. gallinarum especially appeared to be beneficially associated with reproductive-related indicators (FSH, E2, AMH, PRL) whilst L. iners appeared to have a detrimental effect. The result of the present study may enable the identification of microbiota associated with POF, however, further investigations of differences in the microbiota in the context of POF will enable a deeper understanding of the disease pathogenesis that involves modification of the vaginal microbiota. CONCLUSIONS: The present study identified the microbiota associated with POF. Further investigations on the differences in the microbiota in the context of POF will improve our understanding of the pathogenesis of the disease which involves modification of the vaginal microbiota.

Metagenomic analysis identified microbiome alterations and pathological association between intestinal microbiota and polycystic ovary syndrome.

OBJECTIVE: To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes. DESIGN: Cross-sectional study. SETTING: Academic institution. PATIENT(S): Reproductive-aged women with PCOS (n = 14) and controls (n = 14) from the Centre for Reproductive Medicine. INTERVENTION(S): Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis. MAIN OUTCOME MEASURE(S): Identification of different gut microbial strains and relativity between microbiota and clinical parameters. RESULT(S): We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antimüllerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS. CONCLUSION(S): Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice.

Advances in the Application of Biomimetic Endometrium Interfaces for Uterine Bioengineering in Female Infertility.

The Asherman's syndrome, also known as intrauterine adhesion, often follows endometrium injuries resulting from dilation and curettage, hysteroscopic resection, and myomectomy as well as infection. It often leads to scarring formation and female infertility. Pathological changes mainly include gland atrophy, lack of vascular stromal tissues and hypoxia and anemia microenvironment in the adhesion areas. Surgical intervention, hormone therapy and intrauterine device implantation are the present clinical treatments for Asherman's syndrome. However, they do not result in functional endometrium recovery or pregnancy rate improvement. Instead, an increasing number of researches have paid attention to the reconstruction of biomimetic endometrium interfaces with advanced tissue engineering technology in recent decades. From micro-scale cell sheet engineering and cell-seeded biological scaffolds to nano-scale extracellular vesicles and bioactive molecule delivery, biomimetic endometrium interfaces not only recreate physiological multi-layered structures but also restore an appropriate nutritional microenvironment by increasing vascularization and reducing immune responses. This review comprehensively discusses the advances in the application of novel biocompatible functionalized endometrium interface scaffolds for uterine tissue regeneration in female infertility.

Asymmetrical 3D Nanoceria Channel for Severe Neurological Defect Regeneration.

Inflammation and oxidative stress are major problems in peripheral nerve injury. Nanoceria can manipulate antioxidant factor expression, stimulate angiogenesis, and assist in axonal regeneration. We fabricate collagen/nanoceria/polycaprolactone (COL/NC/PCL) conduit by asymmetrical three-dimensional manufacture and find that this scaffold successfully improves Schwann cell proliferation, adhesion, and neural expression. In a 15-mm rat sciatic nerve defect model, we further confirm that the COL/NC/PCL conduit markedly alleviates inflammation and oxidative stress, improves microvessel growth, and contributes to functional, electrophysiological, and morphological nerve restoration in the long term. Our findings provide compelling evidence for future research in antioxidant nerve conduit for severe neurological defects.

Characteristics and management of bone and joint tuberculosis in native and migrant population in Shanghai during 2011 to 2015.

BACKGROUND: China had the third highest burden of tuberculosis population in the world. Bone and joint tuberculosis was a major part and its characteristics were rarely discussed before. This study was designed to review the characteristics and management of bone and joint tuberculosis among native and migrant population in Shanghai, China during 2011-2015. METHODS: A retrospective analysis of the patient clinical records on their demographic information, clinical features and treatment was conducted from three tertiary referral hospitals. Analysis of continuous variables included calculation of the median value with interquartile range. Categorical variables were displayed as percentages and compared using the Fisher's exact test and chi-square test. All continuous variables were compared using Student's unpaired t-test and Mann Whitney U test. RESULTS: One hundred fifteen patients with bone and joint tuberculosis were involved in this study. Native people were generally older (p = 0.003) and had more comorbidities like hypertension (40.74% vs. 16.39%, p = 0.004), diabetes mellitus (38.89% vs. 13.11%, p = 0.001), and cancer (31.48% vs. 14.75%, p = 0.032) than migrants. Migrant patients generally experienced a longer period of uncomfortable feelings before going to doctor than native people (p = 0.007). Spine was a major infection site in comparison with other peripheral joints. Radiological evaluation displayed increased osteolytic reaction in migrant patients compared with native people (p = 0.031). The mean time for anti-tuberculosis treatment was significantly longer in native Shanghai patients (8.96 months vs. 7.94 months, p = 0.003). The curative ratio displayed a significant difference between native and migrant patients (88.24%vs.75.93%, p = 0.009). CONCLUSION: Bone and joint tuberculosis exhibited a poorer outcome in migrant people, who also had longer period of manifestation, more severe osteolytic reaction from CT scan and higher recurrent rate than native people. The surgical treatment in addition to anti-tuberculosis drug therapy had great implications for bone and joint tuberculosis recovery.

Insights into medical humanities education in China and the West.

Medical humanity is the soul of health education. Beginning medical students are taught various aspects of basic medicine, such as biochemistry, anatomy, and immunology. However, cultivation of the humanistic aspects of medicine has received increasing attention in recent decades. We performed a comparison study based on a literature search and our experience with medical humanistic courses in Western and Chinese medical colleges. We found both similarities and disparities in humanities courses offered in Western medical colleges and Chinese medical colleges. The delivery of humanities courses, such as medical sociology, medical ethics, medical psychology, and medical history, is widespread and helps to prepare students for their transformation from medical students to skilful medical professionals. Both Western and Chinese medical colleges offer a variety of medical humanistic courses for undergraduate students. Although Chinese medical humanistic education has undergone major changes, it still requires improvement and educators can learn from Western practice. We hope that our analysis will contribute to education reforms in the medical field.

3D melatonin nerve scaffold reduces oxidative stress and inflammation and increases autophagy in peripheral nerve regeneration.

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.

Surgical release for tubercular elbow stiffness.

BACKGROUND: For decades, tuberculosis (TB) has posed a great threat to people worldwide. Bone and joint TB is one of the most common types of extrapulmonary TB, with elbow TB comprising a small proportion of these cases. The treatment for elbow stiffness associated with TB has been rarely reported. PATIENTS AND METHODS: We retrospectively analyzed six patients (four females and two males) with tubercular elbow stiffness during a 7-year period. All of them received open arthrolysis and hinged external fixation to restore functional extension, flexion, supination and pronation. Mayo Elbow Performance Score (MEPS) and range of motion (ROM) were evaluated preoperatively and at final follow-up. RESULTS: At final follow-up after surgery, we evaluated the average active ROM, which was 111.7° (90°-135°). The average extension was 11.7° (0°-30°), while the average flexion was 123.3° (115°-135°). At the same time, the average supination was increased to 70° (40°-90°) and the average pronation was increased to 68.3° (45°-80°). The MEPS was elevated to 92.5 (85-100). Three patients displayed complications and were treated and cured with dressing changes and antibiotics. CONCLUSION: Open arthrolysis and hinged external fixation are useful for the treatment of non-traumatic elbow stiffness with TB.

An integrated multi-layer 3D-fabrication of PDA/RGD coated graphene loaded PCL nanoscaffold for peripheral nerve restoration.

As a conductive nanomaterial, graphene has huge potentials in nerve function restoration by promoting electrical signal transduction and metabolic activities with unique topological properties. Polydopamine (PDA) and arginylglycylaspartic acid (RGD) can improve cell adhesion in tissue engineering. Here we report an integrated 3D printing and layer-by-layer casting (LBLC) method in multi-layered porous scaffold fabrication. The scaffold is composed of single-layered graphene (SG) or multi-layered graphene (MG) and polycaprolactone (PCL). The electrically conductive 3D graphene scaffold can significantly improve neural expression both in vitro and in vivo. It promotes successful axonal regrowth and remyelination after peripheral nerve injury. These findings implicate that graphene-based nanotechnology have great potentials in peripheral nerve restoration in preclinical and clinical application.

Platelet-Rich Plasma Derived Growth Factors Contribute to Stem Cell Differentiation in Musculoskeletal Regeneration.

Stem cell treatment and platelet-rich plasma (PRP) therapy are two significant issues in regenerative medicine. Stem cells such as bone marrow mesenchymal stem cells, adipose-derived stem cells and periodontal ligament stem cells can be successfully applied in the field of tissue regeneration. PRP, a natural product isolated from whole blood, can secrete multiple growth factors (GFs) for regulating physiological activities. These GFs can stimulate proliferation and differentiation of different stem cells in injury models. Therefore, combination of both agents receives wide expectations in regenerative medicine, especially in bone, cartilage and tendon repair. In this review, we thoroughly discussed the interaction and underlying mechanisms of PRP derived GFs with stem cells, and assessed their functions in cell differentiation for musculoskeletal regeneration.