Growth factors play an important role in wound healing, and they mainly accelerate wound healing by activating the related signal pathways. Chinese scientists have been conducting basic and clinical researches on growth factors for 30 years, with a series of growth factor drugs being developed and widely used in the treatment of burns and trauma and chronic refractory ulcers. This paper expounds the frontier progress of growth factors on wound healing from the perspectives of immunity, nerve, fat, and so on, and puts forward the further thoughts of the research team on the regulation of wound healing by growth factors.
Burns/therapy* ; Humans ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Signal Transduction ; Wound Healing

Wound repair is a highly coordinated and mutually regulated complex process involving various kinds of cells, extracellular matrices and cytokines. A variety of growth factors play an important regulatory role in wound healing, and it is critical to achieve effective delivery and sustained function of growth factors. In recent years, the application of biomaterials in tissue engineering has shown great potential, and the effective delivery of growth factors by biomaterials has attracted increasing attention. Based on this, this paper introduces the mechanism of related growth factors in the process of wound healing, focusing on the recent progress of biomaterial delivery of growth factors to accelerate wound healing, in order to provide new enlightenment for clinical wound treatment.
Biocompatible Materials/metabolism* ; Extracellular Matrix/metabolism* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Tissue Engineering ; Wound Healing

BACKGROUNDCollapsin response mediator protein-2 (CRMP2), a multifunctional cytosolic protein highly expressed in the brain, is degraded by calpain following traumatic brain injury (TBI), possibly inhibiting posttraumatic neurite regeneration. Lipid peroxidation (LP) is involved in triggering postinjury CRMP2 proteolysis. We examined the hypothesis that propofol could attenuate LP, calpain-induced CRMP2 degradation, and brain injury after TBI.

METHODSA unilateral moderate controlled cortical impact injury was induced in adult male Sprague-Dawley rats. The animals were randomly divided into seven groups: Sham control group, TBI group, TBI + propofol groups (including propofol 1 h, 2 h, and 4 h groups), TBI + U83836E group and TBI + fat emulsion group. The LP inhibitor U83836E was used as a control to identify that antioxidation partially accounts for the potential neuroprotective effects of propofol. The solvent of propofol, fat emulsion, was used as the vehicle control. Ipsilateral cortex tissues were harvested at 24 h post-TBI. Immunofluorescent staining, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were used to evaluate LP, calpain activity, CRMP2 proteolysis and programmed cell death. The data were statistically analyzed using one-way analysis of variance and a paired t-test.

RESULTSPropofol and U83836E significantly ameliorated the CRMP2 proteolysis. In addition, both propofol and U83836E significantly decreased the ratio of 145-kDa αII-spectrin breakdown products to intact 270-kDa spectrin, the 4-hydroxynonenal expression and programmed cell death in the pericontusional cortex at 24 h after TBI. There was no difference between the TBI group and the fat emulsion group.

CONCLUSIONSThese results demonstrate that propofol postconditioning alleviates calpain-mediated CRMP2 proteolysis and provides neuroprotective effects following moderate TBI potentially by counteracting LP and reducing calpain activation.

Animals ; Blotting, Western ; Brain Injuries ; drug therapy ; metabolism ; Calpain ; metabolism ; Intercellular Signaling Peptides and Proteins ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Nerve Tissue Proteins ; metabolism ; Propofol ; therapeutic use ; Proteolysis ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of Osteoking on bone mineral density (BMD) and serum Dickkopf-1 (DKK-1) protein levels in rabbits with osteoporotic fracture (OPF).

METHODSTotally 45 female Japanese big-ear rabbits were randomly divided into the treatment group, the model group, and the blank control group (as the control group), 15 in each group. Bilateral ovaries were ectomized for 24 weeks in the treatment group and the model group. Their left radial factures were induced after confirmed osteoporosis. Rabbits in the treatment group were administered with Osteoking by gastrogavage, once per two days. Equal volume of normal saline was given to rabbits in the model group. The general BMD and serum DKK-1 protein levels were detected before ovariectomy, at week 24 and 48 after ovariectomy.

RESULTSThere was significant difference in the general BMD at week 24 after ovariectomy between the model group and the control group, and it was lower in the model group. Compared with the model group, the general BMD significantly increased and serum DKK-1 protein levels significantly decreased in the treatment group after intervention. Serum DKK-1 protein levels were significantly lower after intervention than before intervention in the treatment group.

CONCLUSIONOsteoking could improve the BMD of OPF rabbits, and reduce their serum DKK-1 protein levels as well.

Animals ; Bone Density ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Osteoporosis ; Osteoporotic Fractures ; drug therapy ; metabolism ; Ovariectomy ; Rabbits

AIM: To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae). METHODS: The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. RESULTS: Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1IIIB, HIV-1A17, and HIV-19495, induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng·mL⁻¹. Wikstroelide M also had high inhibitory activities against HIV-2ROD and HIV-2CBL-20-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng·mL⁻¹. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng·mL⁻¹. Wikstroelide M also potently inhibited HIV-1IIIB induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng·mL⁻¹. The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. CONCLUSION Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75.
Anti-HIV Agents ; pharmacology ; therapeutic use ; Cell Line ; Daphne ; chemistry ; Diterpenes ; pharmacology ; HIV Infections ; drug therapy ; virology ; HIV Integrase ; metabolism ; HIV Integrase Inhibitors ; pharmacology ; therapeutic use ; HIV Reverse Transcriptase ; antagonists & inhibitors ; HIV-1 ; drug effects ; enzymology ; HIV-2 ; drug effects ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Virus Integration ; drug effects ; Virus Replication ; drug effects

OBJECTIVEBased on the observation that coagulation necrosis occurs in the majority of neonatal necrotizing enterocolitis (NEC) patients, it is clear that intestinal ischemia is a contributing factor to the pathogenesis of NEC. However, the published studies regarding the role of intestinal ischemia in NEC are controversial. The aim of this paper is to review the current studies regarding intestinal microcirculatory dysfunction and NEC, and try to elucidate the exact role of intestinal microcirculatory dysfunction in NEC.

DATA SOURCESThe studies cited in this review were mainly obtained from articles listed in Medline and PubMed. The search terms used were "intestinal microcirculatory dysfunction" and "neonatal necrotizing enterocolitis".

STUDY SELECTIONMainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.

RESULTSImmature regulatory control of mesentery circulation makes the neonatal intestinal microvasculature vulnerable. When neonates are subjected to stress, endothelial cell dysfunction occurs and results in vasoconstriction of arterioles, inflammatory cell infiltration and activation in venules, and endothelial barrier disruption in capillaries. The compromised vasculature increases circulation resistance and therefore decreases intestinal perfusion, and may eventually progress to intestinal necrosis.

CONCLUSIONIntestinal ischemia plays an important role through the whole course of NEC. New therapeutic agents targeting intestinal ischemia, like HB-EGF, are promising therapeutic agents for the treatment of NEC.

Endothelin-1 ; physiology ; Endothelium, Vascular ; physiopathology ; Enterocolitis, Necrotizing ; drug therapy ; etiology ; pathology ; Heparin-binding EGF-like Growth Factor ; Humans ; Infant, Newborn ; Intercellular Signaling Peptides and Proteins ; therapeutic use ; Intestines ; blood supply ; Ischemia ; complications ; Microcirculation ; physiology ; Nitric Oxide ; physiology ; Splanchnic Circulation

This study was aimed to investigate the effect of bortezomib combined with bisphosphonates on serum levels of DKK-1 and RANKL in multiple myeloma patients, and to evaluate its role in the therapy of osteolytic lesion. Fourty-three patients with newly diagnosed and relapsed myeloma were divided into 2 groups. Twenty-three patients were treated with bortezomib combined with bisphosphonates (A group) and 20 patients were treated with bisphosphonates combined with traditional chemotherapy (B group). Serum levels of DKK-1 and RANKL were measured by ELISA before and after 4 cycles of chemotherapy. The results indicated that serum DKK-1 level significantly decreased in patients of A group (43.2 µg/L before vs 30.4 µg/L after 4 cycles of chemotherapy), and so did for serum RANKL level in A group (0.83 pmmol/L before vs 0.45 pmmol/L after 4 cycles of chemotherapy). While there was no significant differences in DKK-1 and RANKL serum level before therapy between A and B groups, but there was significant differences in DKK-1 and RANKL levels after 4 cycles of chemotherapy (P < 0.05). It is concluded that bortezomib combined with bisphosphonates obviously reduce the serum levels of DKK-1 and RANKL, thus has beneficial effect on osteolytic lesion.
Adult ; Aged ; Boronic Acids ; administration & dosage ; therapeutic use ; Bortezomib ; Diphosphonates ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; Pyrazines ; administration & dosage ; therapeutic use ; RANK Ligand ; blood

BACKGROUNDAs two novel adipocytokines, chemerin and apelin play a key role in the pathological process of insulin resistance (IR), glucose metabolism and obesity, researchers have found that the levels of chemerin and apelin changed significantly in type 2 diabetic patients with obesity, however, the underlying mechanism involved remains unclear. The aim of this study was to investigate whether chemerin and apelin play an important role in the pathophysiologic proceeding of diabetes.

METHODSThis study enrolled 81 newly diagnosed obese type 2 diabetes mellitus (T2DM) patients (T2DM group, n = 81). All the patients were randomly assigned to DM1 group treated with metformin (n = 41) and DM2 group treated with pioglitazone (n = 40). After hypoglycemic agents treatment, patients under better blood glucose control were chosen to be given antioxidant treatment. Another 79 subjects without T2DM were recruited as normal control group (NC group), including 40 subjects (NC1 group) with normal body mass index (BMI) and 39 obese subjects (NC2 group). Levels of chemerin, apelin, BMI, tumor necrosis factor-α (TNF-α), homeostasis model assessment of IR (HOMA-IR) and 8-isoprotaglandim F2α (8-iso-PGF2α) were examined at baseline and post-treatment. The relationship between chemerin, apelin and BMI, TNF-α, HOMA-IR, 8-iso-PGF2α was analyzed.

RESULTSThe baseline levels of chemerin, apelin, TNF-α, HOMA-IR and 8-iso-PGF2α in T2DM group were significantly higher than normal control group (P < 0.001). All indices mentioned above were significantly decreased after treatment (P < 0.05). In T2DM patients treated with pioglitazone, indices mentioned above except for HOMA-IR, were decreased significantly compared with patients treated with metformin (P < 0.05). After antioxidant treatment using lipoic acid, levels of chemerin, apelin, TNF-α and 8-iso-PGF2α were further significantly decreased (P < 0.05). Correlation analysis showed that the levels of chemerin and apelin correlated positively with BMI, TNF-α, HOMA-IR and 8-iso-PGF2α before and after treatment with hypoglycemic agents (P < 0.01). The levels of chemerin and apelin also had positive correlation with TNF-α and 8-iso-PGF2α after antioxidant treatment (P < 0.05).

CONCLUSIONSThe levels of chemerin and apelin in obese T2DM patients are closely related to IR. The increased levels may be a result of compensatory response to IR, and also may be the causative factor of IR. The levels of chemerin and apelin correlate closely with oxidative stress and inflammation. The two adipokines may be inflammatory factors playing important roles in the initiation and development of obese T2DM. Chemerin and apelin are related to the pathophysiology of IR, oxidative stress and inflammation.

Apelin ; Blood Glucose ; metabolism ; Body Mass Index ; Chemokines ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; immunology ; metabolism ; Dinoprost ; analogs & derivatives ; metabolism ; Humans ; Hypoglycemic Agents ; therapeutic use ; Inflammation ; metabolism ; Intercellular Signaling Peptides and Proteins ; metabolism ; Metformin ; therapeutic use ; Thiazolidinediones ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

Biologic augmentation could promote rotator cuff tendon healing and improve the mechanical properties as well as reduce postoperative adhesion. Biologic augmentations play a vital role in rotator cuff repair and healing. However, most of the studies were performed on animals and clinical outcomes were short-term follow-up. The therapeutic effects should be assessed in multicenter prospective trials.
Animals ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; therapeutic use ; Rotator Cuff ; metabolism ; pathology ; transplantation ; Rotator Cuff Injuries ; Transplantation ; Wound Healing

OBJECTIVETo explore the difference of effects of two regimens (bortezomib and dexamethasone, BD; and thalidomide and dexamethasone, TD) on bone disease in multiple myeloma (MM).

METHODSForty patients with newly diagnosed and refractory or relapsed MM were treated with BD or TD regimens from Dec 2006 to Sep 2008. Bone pain score and X-ray examination were carried out before and after therapy. Serum levels of DKK-1, sRANKL, OPG and TRACP-5b were measured by ELISA before and 3 months after therapy.

RESULTSSerum TRACP-5b concentration was significantly decreased in patients received TD regimen (5.94 U/L before therapy vs 4.84 U/L 3 months after therapy, P < 0.05), and so did for serum DKK-1 concentration in patients responded to BD regimen (35.11 µg/L before vs 32.03 µg/L 3 months after therapy, P < 0.05); for serum concentration of sRANKL in patients responded to BD regimen (1.05 pmol/L before vs 0.67 pmol/L 3 months after therapy, P < 0.05); and for serum concentration of TRACP-5b in responders to BD regimen (5.57 U/L before therapy vs 4.90 U/L 3 months after therapy, P < 0.05).

CONCLUSIONBortezomib lowers levels of serum DKK-1 and RANKL in responders, thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption. Thalidomide decreases bone resorption regardless of treatment response.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bone Resorption ; drug therapy ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; RANK Ligand ; blood ; Thalidomide ; administration & dosage