Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Ability of serum annexin A1 to predict 6-month poor clinical outcome following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Annexin A1 might be neuroprotective and serum annexin A1 concentrations were markedly declined after severe traumatic brain injury. We determine dthe ability of serum annexin A1 to assess severity and predict prognosis after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We included 157 aSAH patients and 157 healthy subjects. Serum annexin A1 measurements were measured. A poor outcome was designated as Glasgow outcome scale score of 1-3. Multivariate logistic regression analysis was applied to identify predictors of a poor 6-month outcome. RESULTS: Serum annexin A1 concentrations were significantly lower in patients than in controls. Annexin A1 concentrations were strongly correlated with the World Federation of Neurological Surgeons scale (WFNS) score, Hunt-Hess score, Glasgow coma scale score and modified Fisher score. A total of 59 patients (37.6%) experienced a poor outcome. Serum annexin A1, WFNS score and modified Fisher score emerged as the 3 independent predictors for a poor outcome after aSAH. Under ROC curve analysis, serum annexin A1 had a fair accuracy to predict a poor outcome, AUC of serum annexin A1 concentration was equivalent to those of WFNS score and modified Fisher score and AUC of combination of the 3 factors significantly exceeded that of each one alone. CONCLUSIONS: Annexin A1 may be involved in the occurrence and progression of secondary brain injury after aSAH. Detection of serum annexin A1 may have certain ability for assessment of severity and prediction of long-term prognosis following aSAH.

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage.

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1ß, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

Potential role of serum substance P as a favorable biomarker of functional outcome in acute spontaneous intracerebral hemorrhage.

BACKGROUND: Substance P (SP) is implicated in brain inflammation. We clarified relationship between serum SP concentrations and functional outcome of acute intracerebral hemorrhage (ICH). METHODS: We quantified admission serum SP concentrations in 106 ICH patients. The primary outcome measure was a poor outcome at 90 days (modified Rankin Scale score ≥ 3) after onset. RESULTS: Patients with a poor outcome compared with the rest had substantially higher serum SP concentrations. The area under the curve for serum SP concentrations with regard to discriminating a poor outcome was 0.795 (95% CI, 0.706 to 0.867). Serum SP concentrations >449 pg/ml predicted the risk of a poor outcome with 63.0% sensitivity and 78.9% specificity, and were independently associated with a poor outcome (odds ratio, 5.437; 95% CI, 2.156 to 13.715). There were the positive associations between serum SP concentrations, National Institutes of Health Stroke Scale score (r = 0.480), hematoma volume (r = 0.464) and serum C-reactive protein concentrations (r = 0.398). CONCLUSIONS: Higher serum SP concentrations in the acute phase of ICH were intimately associated with aggravated inflammation response, rising severity and increased risk of a poor functional outcome, suggesting that serum SP could be an inflammatory prognostic factor for ICH.

[Effects of Shengmai injection on testicular injury after torsion/detorsion in rats of different ages].

OBJECTIVE: To investigate the different effects of Shengmai injection on testicular injury after testis torsion/detorsion in rats of different ages. METHODS: Sixteen healthy male SD rats aged 3, 6 and 12 weeks were equally randomized into an experimental group (testicular torsion/detorsion plus Shengmai injection) and a control group (testicular torsion/detorsion plus saline). The rat models of testicular torsion were killed 24 h after surgery for the measurement of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis. RESULTS: Compared with the controls, the 3- and 6-week-old rats of the experimental group showed no significant changes in T-AOC, SOD activity and MDA content (P > 0.05), while the 12-week-old experimental rats exhibited a remarkable increase in SOD and T-AOC and an obvious decrease in MDA content (P < 0.05). CONCLUSION: Shengmai injection has a protective effect against acute ischemia-reperfusion testicular injury after torsion/detorsion in rats, but the effect varies with the age, more obvious in older ones.

Effects of aging and hypoxia-inducible factor-1 activity on angiogenic cell mobilization and recovery of perfusion after limb ischemia.

Ischemia is a stimulus for production of angiogenic cytokines that activate local vascular cells and mobilize angiogenic cells to the circulation. These responses are impaired in elderly patients with peripheral arterial disease. Hypoxia-inducible factor (HIF)-1 mediates adaptive responses to ischemia, including production of angiogenic cytokines. In this study, we demonstrate that aging and HIF-1 loss-of-function impair the expression of multiple angiogenic cytokines, mobilization of angiogenic cells, maintenance of tissue viability, and recovery of limb perfusion following femoral artery ligation. We show that HIF-1 directly activates transcription of the gene encoding stem cell factor and that mice lacking the cognate receptor C-KIT have impaired recovery from ischemia. Administration of AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, improved the recovery of perfusion in older mice to levels similar to those in young mice. Injection of AdCA5 into nonischemic limb was sufficient to increase the number of circulating angiogenic cells. These results indicate that HIF-1 activity is necessary and sufficient for the mobilization of angiogenic cells and that HIF-1alpha gene therapy can counteract the pathological effects of aging in a mouse model of limb ischemia.

Spontaneous transformation of cultured mouse bone marrow-derived stromal cells.

Bone marrow-derived stromal cells have engendered interest because of their therapeutic potential for promoting tissue vascularization and repair. When mononuclear cells isolated from mouse bone marrow were cultured in DMEM supplemented with 10% fetal bovine serum, cell populations arose that showed rapid proliferation and loss of contact inhibition. These cells formed invasive soft tissue sarcomas after i.m. injection into nude or scid mice. I.v. injection resulted in the formation of tumor foci in the lungs. The tumors were transplantable into syngeneic immunocompetent mice. Direct injection of cultured cells into immunocompetent mice also resulted in tumor formation. Karyotype analysis showed that increased chromosome number and multiple Robertsonian translocations occurred at passage 3 coincident with the loss of contact inhibition. The remarkably rapid malignant transformation of cultured mouse bone marrow cells may have important implications for ongoing clinical trials of cell therapy and for models of oncogenesis.

Expression of vascular endothelial growth factor receptor 1 in bone marrow-derived mesenchymal cells is dependent on hypoxia-inducible factor 1.

Bone marrow-derived cells are recruited to sites of ischemia, where they promote tissue vascularization. This response is dependent upon the expression of vascular endothelial growth factor (VEGF) receptor 1 (VEGFR1), which mediates cell migration in response to VEGF or placental growth factor (PLGF). In this study, we found that exposure of cultured mouse bone marrow-derived mesenchymal stromal cells (MSC) to hypoxia or an adenovirus encoding a constitutively active form of hypoxia-inducible factor 1 (HIF-1) induced VEGFR1 mRNA and protein expression and promoted ex vivo migration in response to VEGF or PLGF. MSC in which HIF-1 activity was inhibited by a dominant negative or RNA interference approach expressed markedly reduced levels of VEGFR1 and failed to migrate or activate AKT in response to VEGF or PLGF. Thus, loss-of-function and gain-of-function approaches demonstrated that HIF-1 activity is necessary and sufficient for basal and hypoxia-induced VEGFR1 expression in bone marrow-derived MSC.

Effects of gene delivery on collateral development in chronic hypoperfusion: diverse effects of angiopoietin-1 versus vascular endothelial growth factor.

OBJECTIVES: The aim of this research was to test the effects of vascular endothelial growth factor (VEGF)/angiopoietin-1 (Ang-1) on adult hypoperfused tissues. BACKGROUND: Angiopoietin-1 and VEGF act separately and synergistically in vascular development during embryogenesis. However, little is known regarding their relative roles in collateral development after chronic arterial obstruction and tissue ischemia in the adult. METHODS: Central and caudal ear arteries of 32 rabbits were ligated to induce ischemia. At two months, when flow was about 65% of pre-ligation values, we injected intradermally 10(9) plaque-forming unit adenovirus with the following transgenes: Ang-1, VEGF, or a combination of both. Ear perfusion was followed up for four weeks, and vessel leakage was assessed by Evens Blue test. RESULTS: Before injection, flow was 65% of baseline, and endogenous VEGF levels in ischemic tissue were increased. Adenovirus-encoding VEGF gene (Ad.VEGF) at one week caused a visible inflammatory response associated with a 24% flow increase (p = 0.018). Adenovirus-encoding Ang-1 gene (Ad.Ang-1) increased flow 22% (p = 0.004) with no visible inflammation; Ad.VEGF caused three times as much vessel leakage as Ad.Ang-1 (142.5 +/- 38 vs. 49.5 +/- 9.8 ng Evens Blue/mg tissue; p < 0.001). However, at four weeks, compared with baseline, VEGF decreased flow 18% (p = 0.004), whereas Ang-1 increased tissue perfusion 26% (p < 0.001). This effect was abolished when Ad.Ang-1 was injected with soluble VEGF receptor [Ad.Flt(1-3)-Fc], which blocks VEGF-dependent signaling. Exogenous Ang-1 did not increase perfusion in a normally perfused ear, in which endogenous VEGF is not expressed. CONCLUSIONS: Exogenous Ang-1 enhances perfusion in hypoperfused tissues only in the presence of increased levels of endogenous VEGF. Overexpression of VEGF, however, after causing an inflammatory response, does not improve collateral blood flow.

Akt controls vascular smooth muscle cell proliferation in vitro and in vivo by delaying G1/S exit.

Constitutive activation of serine/threonine kinase Akt causes uncontrolled cell-cycle progression in different cell types and in malignancy. To investigate how Akt activation modulates cell-cycle progression in vascular smooth muscle cells (SMCs) in vitro and in the intact animal, we inhibited Akt-dependent signaling by adenovirus-mediated transfection of a dominant-negative Akt mutant (AA-Akt). We observed reduced proliferation rate (P<0.01), DNA synthesis (P<0.01), and a significant arrest in G1/S exit (P<0.01) both in vitro in response to serum stimulation and in vivo after vascular injury. In vivo transfection of the balloon-injured vessel with AA-Akt reduced SMC proliferation, resulting in decreased neointima compared with control virus (P<0.01). These effects were at least in part modulated, both in vitro and in vivo, by increased p21Cip1 expression, as demonstrated by lack of effect of AA-Akt on cell proliferation in p21-/- mouse SMCs. In conclusion, this study demonstrates that Akt-dependent signaling enhances cell-cycle progression of nontransformed SMCs in vitro and in response to vascular injury in the intact animal. These results suggest a role for Akt signaling in modulating the response of normal tissues to stress and the response of the arterial wall to acute and possibly repetitive injuries that ultimately contribute to restenosis and atherosclerosis.

IL-6 is produced by splenocytes derived from CMV-infected mice in response to CMV antigens, and induces MCP-1 production by endothelial cells: a new mechanistic paradigm for infection-induced atherogenesis.

Atherosclerosis is an inflammatory disease. One of the candidate inflammatory triggers is infection. To further characterize the interaction between infection, cytokine induction, and atherosclerosis, we tested the hypothesis that cytomegalovirus (CMV) infection induces the pro-inflammatory cytokine interleukin-6 (IL-6), which in turn induces "pro-atherosclerotic" changes in vascular endothelial cells (ECs). ELISA was used to determine the levels of monocyte chemoattractant protein-1 (MCP-1) in the supernatant of mouse and human ECs incubated with IL-6, and IL-6 levels in supernatants of splenocytes, derived from CMV-infected and uninfected mice, stimulated with mice CMV antigens. IL-6 induced, in a dose response fashion, MCP-1 expression in human ECs: 0, 2, 10, and 50 pg/ml IL-6 increased MCP-1 levels in EC conditioned medium from 1120+/-65 to 1148+/-105, 1395+/-40, and 2119+/-130 pg/ml, respectively (P<0.001). IL-6 also induced MCP-1 expression in mouse ECs (P<0.002). Importantly, IL-6 concentration in the supernatants of splenocytes stimulated with CMV antigens rose from undetectable levels in uninfected mice to 14.9+/-5 pg/ml in the infected mice (P<0.04). These results suggest a previously unrecognized, but potentially important mechanism whereby CMV, and other pathogens, contribute to atherogenesis: T lymphocytes, clonally expanded in response to antigens presented by CMV infection, home to sites of vascular injury and locally release IL-6 when presented with either pathogen antigens that may be present in the plaque, or when they cross-react with host peptides homologous to the relevant pathogen antigens; IL-6 then triggers ECs to release MCP-1, which recruits more monocytes and T-cells into the vessel wall and thereby exacerbates local inflammation, and thus atherogenesis.

Effects of MF-tricyclic, a selective cyclooxygenase-2 inhibitor, on atherosclerosis progression and susceptibility to cytomegalovirus replication in apolipoprotein-E knockout mice.

OBJECTIVES: We examined whether selective cyclooxygenase-2 (COX-2) inhibition in apolipoprotein-E (apoE) deficient mice reduces cytomegalovirus (CMV) replication, and determined whether COX-2 anti-inflammatory activity leads to decreased atherosclerosis. BACKGROUND: Evidence suggests that CMV infection contributes to atherosclerosis and that this occurs in part through inflammatory mechanisms. Cyclooxygenase-2 inhibitors are potent anti-inflammatory agents. They also inhibit CMV replication in vitro. METHODS: The apoE deficient mice were either treated or not treated with a selective COX-2 inhibitor, and either infected or not infected with CMV. Viral deoxyribonucleic acid load in salivary glands was determined by quantitative polymerase chain reaction. Atherosclerotic lesion analysis was performed by standard methods. RESULTS: In vivo COX-2 inhibition, unexpectedly increased viral load: in the CMV-infected animals viral load was 2.58 +/- 1.0 in the nontreated group, 4.74 +/- 1.38 in the group treated with 12 mg/kg/day MF-tricyclic, and 6.51 +/- 1.64 in the group treated with 24 mg/kg/day MF-tricyclic (p trend = 0.050). This increased viral load was paralleled by increased anti-CMV antibody titers. Most surprisingly, COX-2 inhibition significantly increased early atherosclerotic lesion area, independent of viral infection. CONCLUSIONS: Our study demonstrates that selective inhibition of COX-2 in vivo increases viral load. The finding that inhibition of COX-2 increases atherosclerosis development in apoE deficient mice suggests, unexpectedly, that this enzyme exerts antiatherosclerosis activity, at least in this model.