Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

The protective effect of manganese superoxide dismutase from thermophilic bacterium HB27 on hydrochloric acid-induced chemical cystitis in rats.

PURPOSE: To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. METHODS: Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. RESULTS: Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. CONCLUSIONS: Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.

Effect of glycated hemoglobin index and mean arterial pressure on acute ischemic stroke prognosis after intravenous thrombolysis with recombinant tissue plasminogen activator.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

[Analysis of fatal risk factors for severe acute pancreatitis: a report of 141 cases].

OBJECTIVE: To investigate the risk factors affecting the mortality of severe acute pancreatitis (SAP). METHODS: The clinical data of 141 patients with SAP treated from January 2001 to October 2005 were analyzed retrospectively. All the patients were divided into 2 groups, the death group and the survival group. Fifteen potential factors influencing the prognosis of SAP were analyzed with Logistic regression analysis. RESULTS: Thirty-four cases (24.1%) among the 141 patients died. There were significant differences between the two groups in age, body mass index, length of stay, APACHE II score, multiple organ dysfunction syndrome (MODS) and abdominal compartment syndrome (ACS) (P < 0.05). Multiple-factor Logistic regression analysis indicated that the MODS (OR = 67. 358, P < 0.01), APACHE II score (OR =9.716, P < 0.01) and ACS (OR = 5.775, P < 0.05) were the independent risk factors affecting the prognosis of SAP during its early stage, whereas pancreatic infection (OR = 9.652, P < 0.01), MODS (OR = 5.212, P < 0.05) and celiac hemorrhage (OR = 4.707, P < 0.05) were the independent risk factors during the advanced stage of SAP. CONCLUSIONS: MODS,especially respiratory dysfunction and renal dysfunction,is the main cause of early mortality for SAP, whereas infection, multiple organ dysfunction and celiac hemorrhage may impact the later mortality. Therefore early prevention and correct management on the risk factors play critical roles in reducing the mortality of SAP.

[Study of effect and mechanism of c-myb on the fertilization in mouse].

AIM: To investigate the distribution of c-myb, an oncoprotein, in mouse oocytes-cumulus cell complex and sperm immunohistochemically. METHODS: To study the effect of c-myb on mouse fertilization in vitro, various concentration of c-myb antisense-oligodeoxynucleotides (c-myb ASODNs) were incubated with sperms and oocytes during fertilization. To explore the possible mechanism involved in fertilization, the relationship between c-myb ASODNs and GABA or dbcAMP or Verapamil or Progesterone in fertilization was also observed by immunohistochemical methods. RESULTS: c-myb oncoprotein was observed on the nucleus of cumulus cell and head of sperm. c-myb ASODNs inhibited the rate of fertilization in vitro in a dose-dependent way. The fertilization rates of the control group, low (5 micromol/L), medium (10 micromol/L), high (20 micromol/L) concentration c-myb ASODNs groups and nonsense tat oligodeoxynucleotides (20 micromol/L) group were 34.97%, 30.89%, 20.14%, 16.68%, 34.47%, respectively. All of GABA, Progesterone and dbcAMP inversed the c-myb ASODNs inhibition effects on fertilization rate, but neither of them showed significant effect on the percentages of immunohistochemical stain of Myb on sperm and cumulus cells. By contrast, Verapamil inhibited the fertilization rate. Co-treated with c-myb ASODNs, Verapamil showed synergic inhibiting effects on the fertilization with c-myb ASODNs. Verapamil also inhibited the expression of Myb on head of sperm. The fertilization rates of the control group, medium (10 micromol/L) concentration c-myb ASODNs group, GABA group, P4 group, Verapamil group, dbcAMP group were 34.81%, 22.96%, 40.83%, 39.12%, 7.46%, 40.61%, respectively. CONCLUSION: c-myb ASODNs is closely correlated with fertilization. Verapamil can inhibit fertilization in vitro through regulating Myb expression of sperm, while GABA, dbcAMP and Verapamil may affect the process of fertilization through the way other than Myb expression.

[Experimental study of c-erbB2 on the fertilization in mouse].

AIM AND METHODS: The distribution of ErbB2 in mouse testis, epididymidis, ovaries, oocyte-cumulus cells-complexes in oviducts and sperms was investigated immunohistochemically. To study the effect of c-erbB2 on mouse fertilization in vitro, various concentrations of c-erbB2 antisense oligonucleotides (c-erbB2 ASODNs) were incubated with sperms and oocyte-cumulus cells-complexes during fertilization in vitro. To explore possible mechanisms involved in fertilization, the relationship between c-erbB2 ASODNs and GABA, or dbcAMP, or verapamil during fertilization in vitro was also observed. RESULTS: ErbB2 oncoprotein was observed in epithelial cells in epididymis, sperms and cumulus cells. C-erbB2 ASODNs inhibited the rate of fertilization in vitro in a dose-dependent way. The fertilization rate of the control group, low (5 micromol/L), medium (10 micromol/L), high (20 micromol/L) concentration c-erbB2 ASODNs group, and nonsense at oligonucleotides group (20 micromol/L) was 38.3%, 19.6%, 10.7%, 5.0%, and 33.8% respectively. Integral optical density immunostaining of ErbB2 in sperms was notably reduced. Medium and high concentration of c-erbB2 ASODNs notably inhibited cumulus cells adhering to inner wall of Petri dish. Treated alone with GABA or dbcAMP, the rate of fertilization was increased. Both GABA and dbcAMP partially inversed the ASODNs inhibition effect on fertilization rate, but neither of them showed significant effect on sperm integral optical density of ErbB2 immunostaining. In contrast, verapamil inhibited fertilization rate. Co-treated with c-erbB2 ASODN, verapamil showed synergic inhibiting effect on fertilization with c-erbB2 ASODN. Verapamil also inhibited the expression of c-erbB2 in sperms. CONCLUSION: It is suggested that c-erbB2 is closely correlated with fertilization. Ca2+ may inhibit fertilization in vitro through regulation the expression of c-erbB2 gene in sperm cells, while both of GABA and dbcAMP may affect the process of fertilization through the way other than c-erbB2 expression in sperm cells.

[Expression of c-fos in various functional state of rat ovaries].

AIM AND METHODS: The method of labeled streptavidin biotin was used to study the expression of c-fos in various functional state of rat ovaries and its relationship with the levels of serum estradiol and progesterone. RESULTS: (1) In the mature rat, c-fos expression was found higher in interstitial gland and stroma of proestrous ovaries and lower in estrous ovaries, and was found higher in luteal cells and stroma of pregnant ovaries and lower in diestrous ovaries. There was a positive correlation between the area and optical density of c-fos expression and the levels of serum E2 and P. (2) In the immature rats, c-fos expression was not found in the ovaries containing preantral follicles from DES-treated rats,and was found both in interstitial gland and stroma of the ovaries containing preovulatory follicles from PMSG-treated rats ,and the expression was higher in day 4 luteinized ovaries and lower in day 9 luteinized ovaries from PMSG with hCG treated rats. There also was a positive correlation between the area and optical density of c-fos expression and the levels of serum E2 and P. CONCLUSION: The results suggested in rat ovaries and might play an important role in follicles development, ovulation, luteum formation and regression.