This study aims to investigate the efficacy of forsythiaside A(FTA) against CCl_4-induced liver fibrosis and the mechanism. Specifically, activities of serum alanine/aspartate aminotransferase(ALT/AST) and hydroxyproline(HYP) level in liver were detected, and pathological morphology of liver was observed based on hematoxylin-eosin(HE) staining, Masson's trichrome staining, and Sirius red staining of liver. On this basis, the effect of FTA on liver fibrosis was evaluated. The mRNA expression of actin alpha 2/α-smooth muscle actin(Acta2/α-SMA), transforming growth factor β(Tgfβ), collagen Ⅰ alpha 1(Col1 a1), and collagen Ⅲ alpha 1(Col3 a1) in liver tissue and hepatic stellate cells(HSC) was determined by qPCR, and the protein expression of α-SMA in liver tissue and HSC was measured by Western blot to assess the inhibition of FTA on HSC activation. The protein expression of α-SMA, vi-mentin(Vim), vascular endothelial cadherin(Ve-cadherin), and platelet endothelial cell adhesion molecule-1(PECAM-1/CD31) was measured by Western blot to evaluate the reverse of endothelial-mesenchymal transition(EMT) by FTA. The efficacy of FTA in relieving CCl_4-induced liver fibrosis was evidenced by the alleviation of hepatocyte necrosis, liver inflammation, and hepatic collagen deposition. FTA decreased the mRNA expression of Acta2, Tgfβ, Col1 a1, and Col3 a1 and protein expression of α-SMA both in vivo and in vitro. FTA reversed the increase of α-SMA and Vim and the decrease of CD31 and Ve-cadherin in livers from mice treated with CCl_4. Therefore, FTA alleviated CCl_4-induced liver fibrosis in mice via suppressing HSC activation and reversing EMT.
Animals ; Mice ; Actins/metabolism* ; Alanine Transaminase/blood* ; Carbon Tetrachloride/metabolism* ; Collagen/metabolism* ; Hepatic Stellate Cells ; Liver/drug effects* ; Liver Cirrhosis/genetics* ; RNA, Messenger/metabolism* ; Transforming Growth Factor beta/metabolism* ; Glycosides/therapeutic use*

OBJECTIVES: To study the level of serum vitamin K₂ (VitK₂) and its association with bone metabolism markers osteocalcin (OC), type I procollagen amino-terminal peptide (PINP), and type I collagen carboxy-terminal peptide (CTX) in children. METHODS: A prospective analysis was performed on 1 732 children who underwent routine physical examination from October 2020 to October 2021. The serum levels of VitK₂ and 25-hydroxy vitamin D [25(OH)D] were measured. According to age, they were divided into four groups: <1 year, 1-3 years group, >3-6 years group, and >6-14 years. A total of 309 children with 25(OH)D≥50 nmol/L were screened out, and serum levels of OC, PINP, and CTX were measured to investigate the correlation of the serum levels of OC, PINP, and CTX with serum VitK₂ levels in different age groups. RESULTS: The prevalence rate of serum VitK₂ deficiency was 52.31% (906/1 732). The VitK₂ deficiency group had higher prevalence rates of overweight/obesity and growth pain (≥3 years of age) than the normal VitK₂ group (P<0.05). There were differences in the prevalence rate of serum VitK₂ deficiency (P<0.0083) and the serum level of VitK₂ (P<0.05) between the 1-3 years group and the >6-14 years group. The <1 year group had a higher serum level of CTX and a lower serum level of PINP than the >3-6 years group and the >6-14 years group (P<0.05). The <1 year group had a lower serum level of OC than the >6-14 years group (P<0.05). Serum VitK₂ level was positively correlated with OC level (r_s=0.347, P<0.01), and CTX level was negatively correlated with PINP level (r_s=-0.317, P<0.01). CONCLUSIONS Serum VitK₂ deficiency may be associated with overweight/obesity. Serum VitK₂ may affect the level of OC and even bone health.
Child ; Humans ; Infant ; Biomarkers/metabolism* ; Collagen Type I/metabolism* ; Obesity/complications* ; Osteocalcin/metabolism* ; Overweight/complications* ; Peptide Fragments/metabolism* ; Peptides/metabolism* ; Procollagen/metabolism* ; Vitamin K/blood* ; Child, Preschool ; Adolescent ; Bone and Bones/metabolism*

To observe the effect of Fengshi Qutong Capsules(FSQTC) on angiogenesis of rat aortarings and in knee joint synovium of type Ⅱ collagen-induced arthritis(CIA) rats. The blood vessel of aorta rings of normal SD rats were induced by vascular endothelial growth factor(VEGF) 20 μg·L~(-1 )in vitro, and were treated with FSQTC(0.02, 0.1 and 0.5 μg·L~(-1)) continuously for 9 days. The number, length and area of neovascularization of the vascular ring were measured. SD rats were immunized to establish collagen-induced arthritis. CIA rats were treated with FSQTC(0.25, 0.5, 1 g·kg~(-1)·d~(-1)) and methotrexate(0.2 mg·kg~(-1)·d~(-1)) daily for 19 days. Histopathological examination(HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joint. Immunohistochemistry was performed to observe the expression of platelets-endothelial cell adhesion molecule(CD31), VEGF and VEGF receptor 2(VEGFR_2)in the synovium. Immunofluorescence was performed to observe the expression of CD31 and α smooth muscle actin(αSMA) in synovial membrane.TGF-β, PDGF and VEGFR_2 in serum were detected by enzyme-linked immunosorbent assay. The number, branch length and area of blood vessels of aorta rings were significantly increased induced by VEGF, and FSQTC could significantly reduce the number, branch length and area of blood vessels. Compared with the normal group, the vascular density, CD31 positive expression, CD31~+/αSMA~- immature and total vascular positive expression in the synovial membrane of the model group were significantly increased, and so as VEGF and VEGFR_2 in the synovium. The VEGFR_2, TGF-β and PDGF in sera were also significantly increased in model group. FSQTC reduced the synovial vascular density and inhibited the positive expression of CD31, CD31~+/αSMA~- immature blood vessels and total vascular. FSQTC has no significant effect on CD31~+/αSMA~+mature blood vessels. FSQTC also negatively inhibited the expression of VEGF, VEGFR_2, TGF-β and PDGF in synovial membrane and/or sera. The effect of methotrexate is similar with to the high dose group. Our results demonstrated that FSQTC could inhibit the angiogenesis of synovial tissue in CIA rats and of aortaring in rats, which is related to the reduction of angiogenesis regulatory factor.
Animals ; Aorta ; Arthritis, Experimental ; chemically induced ; drug therapy ; Capsules ; Collagen Type II ; Drugs, Chinese Herbal ; pharmacology ; Neovascularization, Pathologic ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane ; blood supply ; Vascular Endothelial Growth Factor A

OBJECTIVE: Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. METHODS: HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin (α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. RESULTS: Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang (1-7) increased the levels of ACE2 and Ang (1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang II. CONCLUSION Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang (1-7)-Mas axis.
Actins ; metabolism ; Angiotensin I ; blood ; pharmacology ; therapeutic use ; Angiotensin II ; blood ; Animals ; Animals, Newborn ; Cell Differentiation ; drug effects ; Cells, Cultured ; Collagen Type I ; metabolism ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Myofibroblasts ; drug effects ; Peptide Fragments ; blood ; pharmacology ; therapeutic use ; Peptidyl-Dipeptidase A ; metabolism ; Rats, Wistar ; Silicosis ; metabolism ; pathology ; prevention & control

Ehlers-Danlos syndrome (EDS) is an inherited disorder of collagen biosynthesis and structure, characterized by skin hyperextensibility, joint hypermobility, aberrant scars, and tissue friability. Besides the skin, skeleton (joint) and vessels, other organs such as the eyes and the intestine can be affected in this syndrome. Accordingly, interdisciplinary cooperation is necessary for a successful treatment. Three basic surgical problems are arising due to an EDS: decreased the strength of the tissue causes making the wound dehiscence, increased bleeding tendency due to the blood vessel fragility, and delayed wound healing period. Surgery patients with an EDS require an experienced surgeon in treating EDS patients; the treatment process requires careful tissue handling and a long postoperative care. A surgeon should also recognize whether the patient shows a resistance to local anesthetics and a high risk of hematoma formation. This report describes a patient with a wide open wound on the foot dorsum and delayed wound healing after the primary approximation of the wound margins.
Anesthetics, Local ; Blood Vessels ; Cicatrix ; Collagen ; Connective Tissue Diseases ; Ehlers-Danlos Syndrome ; Foot ; Hematoma ; Hemorrhage ; Humans ; Intestines ; Joint Instability ; Postoperative Care ; Skeleton ; Skin ; Wound Healing ; Wounds and Injuries

BACKGROUND AND OBJECTIVES: Oral ulceration is one of the most common debilitating condition that affects the oral cavity. In this study, the effect of locally injected platelet rich plasma (PRP) and bone marrow-derived mesenchymal stem cells (BMSCs) on the healing of oral ulcer was investigated. METHODS AND RESULTS: An ulcer was induced in buccal mucosa of rats by using 5mm biopsy punch followed by application of cotton swab soaked with formocresol for 60sec. The ulcer was left untreated in the control group, treated with intralesional injection of PRP, or isolated cultured BMSCs. Data were analyzed clinically, histologically and immunohistologically on day 3, 5, 7 and 10. BMSCs group showed smaller ulcer area throughout the whole experimental period than the other groups with complete resolution of the ulcer on day 10, unlike the control group. However, there was no significant difference with PRP, on day 5, 7 and 10, regarding clinical ulcer size. BMSCs group showed better histological results regarding the rate of epithelial cell migration, the number of inflammatory cells, thickness and organization of collagen fibres and the number of blood vessels, with complete re-epithelization on day 10. BMSCs group showed a greater number of anti-PCNA positive nuclei throughout the whole experimental period than the other groups except on day 5, PRP had higher mean numbers of anti-PCNA positive nuclei in both tissues. CONCLUSIONS: Both PRP and BMSCs accelerate wound healing and enhance the quality of the healing tissue with the latter being slightly more effective and faster.
Animals ; Biopsy ; Blood Platelets ; Blood Vessels ; Bone Marrow ; Collagen ; Epithelial Cells ; Injections, Intralesional ; Mesenchymal Stromal Cells ; Mouth ; Mouth Mucosa ; Oral Ulcer ; Platelet-Rich Plasma ; Rats ; Ulcer ; Wound Healing

Cardiovascular disease is the leading cause of morbidity and mortality worldwide. Early detection of subclinical atherosclerosis is important for reduction of cardiovascular risk. However, the current diagnostic strategy, which focuses on traditional risk factors or the use of risk scoring, is unsatisfactory. Arterial walls thicken and stiffen with age, a process known as arteriosclerosis. There is a close interaction between arterial stiffness and atherosclerosis. Increased luminal pressure and shear stress caused by arterial stiffening result in endothelial dysfunction, accelerate the formation of atheromas, and stimulate excessive collagen production and deposition in the arterial wall. Carotid intima-media thickness (CIMT) has been shown to predict cardiovascular risk in many large studies. However, there is controversy regarding the value of CIMT for prediction of cardiovascular risk because of differences in study design, specifically with respect to CIMT measurements. Pulse wave velocity (PWV) is the most widely used measure of arterial stiffness; measurement of PWV is simple, non-invasive, and reproducible. Many clinical studies and meta-analyses have shown that PWV has predictive value in cardiovascular disease beyond traditional risk factors, both in the general population and in patients with various diseases. Brachial pressure has been a poor surrogate for aortic pressure for more than 50 years. However, recent studies have shown a closer relationship between central blood pressure and intermediate cardiovascular phenotypes or cardiovascular target organ damage, compared to the respective relationships with brachial blood pressure. Considering the non-invasiveness and ability to collect multiple types of clinical data, measurement of CIMT, PWV, and central blood pressure may be useful to identify patients at high risk for development of cardiovascular disease.
Arterial Pressure ; Arteriosclerosis ; Atherosclerosis ; Blood Pressure ; Cardiovascular Diseases ; Carotid Intima-Media Thickness ; Collagen ; Humans ; Mortality ; Phenobarbital ; Phenotype ; Plaque, Atherosclerotic ; Pulse Wave Analysis ; Risk Factors ; Vascular Stiffness

A 61-year-old man presented with a 3-year history of erythematous firm nodules on the hands and feet. Histopathological findings of the lesional skin revealed perivascular and diffuse neutrophilic infiltrations on the upper and mid-dermis. Increased and dilated blood vessels were observed in the upper dermis. Fibrinoid necrosis of the vessel walls was unremarkable, but endothelial swelling and scant red blood cell (RBC) extravasation were noted. Fibrosis and sclerosis of collagen fibers were noted on the deep dermis. Results of laboratory examinations, including complete blood count (CBC), routine chemistry, c-reactive protein (CRP), syphilis and human immunodeficiency virus (HIV) tests, and serum immunoglobulin electrophoresis, were all negative or within normal limit. A diagnosis of erythema elevatum diutinum was made based on the clinical and histological findings. The patient was treated with prednisolone, dapsone, colchicine, and intralesional injection of triamcinolone and showed slight improvement after treatment for 8 months.
Blood Cell Count ; Blood Vessels ; C-Reactive Protein ; Chemistry ; Colchicine ; Collagen ; Dapsone ; Dermis ; Diagnosis ; Electrophoresis ; Erythema ; Erythrocytes ; Fibrosis ; Foot ; Hand ; HIV ; Humans ; Immunoglobulins ; Injections, Intralesional ; Middle Aged ; Necrosis ; Neutrophils ; Prednisolone ; Sclerosis ; Skin ; Syphilis ; Triamcinolone

PURPOSE: The purpose of this study was to evaluate the efficacy of Betafoam in terms of wound healing and safety. METHODS: Fifty-four male adult Sprague-Dawley rats (weight, 200–250 g) were used in the study. Full-thickness skin defects were created on the back of each rats. The rats were assigned to 6 groups according to the type of wound dressing used (n = 9 for each group): Betafoam, Allevyn-Ag, Mepilex-Ag, Medifoam silver, Polymem-Ag, and gauze. The wound size, histological findings, and amount of DNA on the changed dressings for each group were analyzed and compared. RESULTS: All groups showed an effective decrease in wound size. However, the differences between Betafoam and the other dressings were statistically significant on day 14 (P < 0.05). The number of newly generated blood vessels in the Betafoam group was significantly higher than in the gauze, Allevyn-Ag, and Medifoam silver groups (P < 0.001). In the Betafoam group, the proportion of collagen deposition was highest and showed a significantly superior arrangement of collagen fibers compared with the gauze, Allevyn-Ag, Mepilex-Ag, and Medifoam silver groups. The total content of the remaining DNA counts of the exchanged dressings were significantly lower in the Betafoam group than the others. CONCLUSION: Betafoam is effective in wound healing and provides the best performance amongst the various types of dressing materials in terms of re-epithelialization, angiogenesis, collagen deposition, and tissue invasion.
Adult ; Animals ; Bandages ; Blood Vessels ; Collagen ; DNA ; Humans ; Male ; Polyurethanes ; Povidone-Iodine ; Rats ; Rats, Sprague-Dawley ; Re-Epithelialization ; Silver ; Skin ; Wound Healing ; Wounds and Injuries

BACKGROUND: To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. METHODS: In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. RESULTS: The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. CONCLUSIONS: Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications.
Blood Cells ; Bone Marrow* ; Collagen ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Platelet-Rich Plasma ; Rabbits ; Rotator Cuff* ; Shoulder ; Tears* ; Tendons