Icaritin Reduces Oral Squamous Cell Carcinoma Progression via the Inhibition of STAT3 Signaling.

Icaritin, a traditional Chinese medicine, possesses antitumor activity. The current study aimed to investigate icaritin effect and potential mechanism on oral squamous cell carcinoma (OSCC) development. OSCC cells proliferation, apoptosis, and autophagy were analyzed after incubation with icaritin at different concentrations and incubation times. The expressions of proteins related to proliferation, apoptosis, and autophagy, as well as signal transducer and activator of transcription 3 (STAT3) signal network, were also evaluated by western blot. Furthermore, STAT3 was knocked down by siRNA transfection to determine STAT3 role in OSCC cell proliferation and apoptosis. An oral specific carcinogenesis mouse model was used to explore icaritin effect on OSCC in vivo. Icaritin significantly inhibited OSCC proliferation in vitro and reduced the expression of both the cell-cycle progression proteins cyclin A2 and cyclin D1. Besides, icaritin increased cleaved caspase 3 and cleaved poly-(ADP-ribose) polymerase expression leading to apoptosis, and it activated autophagy. Icaritin significantly inhibited the expression of phospho-STAT3 (p-STAT3) in a dose- and time-dependent manner. In the in vivo experiment, the number of malignant tumors in the icaritin-treated group was significantly lower than the control. Overall, icaritin suppressed proliferation, promoted apoptosis and autophagy, and inhibited STAT3 signaling in OSCC in vitro and in vivo. In conclusion, icaritin might be a potential therapeutic agent against OSCC development.

Stable Loading and Delivery of Icaritin Using PEG-PCL Micelles for Effective Treatment of Oral Squamous Cell Carcinoma.

BACKGROUND: Icaritin can inhibit cell proliferation and induce apoptosis in Oral Squamous Cell Carcinoma (OSCC). However, low solubility limits its clinical usage. OBJECTIVES: To improve the efficacy of icaritin treatment, a micelle system was designed for targeted delivery of drugs to OSCC cells. METHODS: In the present study, the micelles loaded with icaritin were self-assembled from the amphipathic polymer via film dispersion. Nanoparticles were characterized with the transmission electron microscope and dynamic light scattering. The cytotoxicity of icaritin nanoparticles was analyzed by CCK-8, and in vitro target-selective intracellular uptake behaviors were observed using a laser confocal microscope. RESULTS: The micelles were spherical with the mean diameter of 121.2 nm. in vitro studies revealed that icaritin was stablely and slowly released from micelles. Cytotoxicity analysis demonstrated that icartin-loaded micelles exhibited better therapeutic efficacy compared with free icaritin. Cellular uptake and intracellular release results revealed that micelles efficiently delivered icaritin into OSCC cells. CONCLUSION: These results suggest that encapsulated icaritin in polycaprolactone - polyethylene glycol (PCL-PEG) micelles may provide safe and effective drug delivery in OSCC treatments.

Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma.

BACKGROUND: Our previous work demonstrated upregulated CD47 in Oral Squamous Cell Carcinoma (OSCC). OBJECTIVE: In the present study, we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms. METHODS: The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified. RESULTS: Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in the apoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knockeddown Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitro phagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling. CONCLUSION: In summary, the knockdown of CD47 downregulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.

Recovery of zinc from hyperaccumulator plants: Sedum plumbizincicola.

Hyperaccumulator biomass harvested after heavy-metal phytoremediation must be considered as hazardous waste that should be contained or treated appropriately before disposal or reuse. As a potential method to detoxify the biomass and to convert this material to a suitable fertilizer or mulch, leaching of heavy metals from Sedum plumbizincicola biomass was studied by using ammonia-ammonium chloride solution as a leaching agent. The research was carried out in two phases: (i) a leaching study to determine the heavy metal:zinc extraction efficiency of this leaching agent and (ii) a thermodynamic analysis to identify the likely reactions and stable Zn(II) species formed in the leaching systems. Experimentally, a Taguchi orthogonal experiment with four variable parameter elements: leaching temperature, nNH4Cl:nNH3 ratio, leaching time and solid-liquid ratio, each at three levels, was used to optimize the experimental parameters by the analysis of variances. Application of the Taguchi technique significantly reduced the time and cost required for the experimental investigation. The findings indicate that leaching temperature had the most dominant effect on metal extraction performance, followed by nNH4Cl:nNH3 ratio, solid-liquid ratio and leaching time. Accordingly, the optimum leaching conditions were determined as temperature: 60 degrees C, nNH4Cl:nNH3 = 0.6, leaching time: 2 h and solid/liquid ratio: 5:1. The total zinc removal after leaching under the optimum conditions reached 97.95%. The thermodynamic study indicated that the dominant species produced by the leaching process should be the soluble species Zn(NH3)4(2+).

Ischemic stroke in patients with POEMS syndrome: a case report and comprehensive analysis of literature.

BACKGROUND: POEMS syndrome is a rare multi-systemic disease characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Arterial or venous thrombosis is a less-common complication of POEMS syndrome. Ischemic stroke has also been reported sporadically. However, the association between POEMS syndrome and ischemic stroke has not been entirely understood. METHODS: A case of ischemic stroke caused by cerebral vasculitis in a patient with POEMS syndrome was presented. Then a comprehensive review and analysis of the literature were performed. RESULTS: A total of 28 patients were identified. The common clinical manifestations of POEMS syndrome were rather non-specific in patients with ischemic stroke compared with those of patients without ischemic stroke. Twenty patients were found with multiple ischemic lesions (71.5%). In the 25 patients who had undergone the evaluation of cerebral arteries, nineteen patients (76.0%) were found with cerebral vasculopathy. Twelve patients (48.0%) had more than one cerebral artery involved. Ischemic events were documented in 8 patients even when they were undergoing all the therapy for ischemic stroke. Ten (55.6%) of the 18 patients who had survival data died within two years after stroke events. CONCLUSION: Comprehensive analysis of literature revealed several trends in patients with ischemic stroke and POEMS syndrome including a low survival rate and a preponderance of cerebral vasculopathy and multiple cerebral arteries affected. Ischemic stroke may be a poor outcome predictor in patients with POEMS syndrome. Further researches focusing on a larger cohort may help in better characterizing and treating this rare complication of POEMS syndrome.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage caused by transverse sinus thrombosis: A case report and review of literature.

RATIONALE: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSAH) is characterized by a pattern of extravasated blood restricted to the perimesencephalic cisterns, normal angiographic findings, and an excellent prognosis with an uneventful course and low risks of complication. The precise etiology of bleeding in patients with PNSAH has not yet been established. The most common hypothesis is that PNSAH is venous in origin. Intracranial venous hypertension has been considered as the pivotal factor in the pathogenesis of PNSAH. The underlying venous pathology such as straight sinus stenosis, jugular vein occlusion may contribute to PNSAH. We describe a patient in whom transverse sinus thrombosis preceded intracranial venous hypertension and PNSAH. These findings supported that the source of the subarachnoid hemorrhage is venous in origin. PATIENT CONCERNS AND DIAGNOSES: A 45-year-old right-handed man was admitted to the hospital with a sudden onset of severe headache associated with nausea, vomiting, and mild photophobia for 6 hours. The patient was fully conscious and totally alert. An emergency brain computed tomography (CT) revealed an acute subarachnoid hemorrhage restricted to the perimesencephalic cisterns. CT angiography revealed no evidence of an intracranial aneurysm or underlying vascular malformation. Digital subtraction angiography of arterial and capillary phases confirmed the CT angiographic findings. Assessment of the venous phase demonstrated right transverse sinus thrombosis. Magnetic resonance imaging confirmed the diagnosis of cerebral venous sinus thrombosis (CVST). Lumbar puncture revealed an opening pressure of 360 mmH2O, suggestive of intracranial venous hypertension. Grave disease was diagnosed by endocrinological investigation. INTERVENTIONS: Low-molecular-weight heparin, followed by oral warfarin, was initiated immediately as the treatment for cerebral venous sinus thrombosis and PNSAH. OUTCOMES: The patient discharged without any neurologic defect after 3 weeks of hospital stay. MR venography revealed recanalization of right transverse sinus at the 6-month follow-up. No clinical or neuroimaging evidence of relapse was detected at 12 months follow-up. LESSONS: Hyperthyroidism may contribute to the development of CVST. The presence of acute transverse sinus thrombosis, as a cause of PNSAH, provides further support for the hypothesis that the source of PNSAH is venous in origin and intracranial venous hypertension plays a critical role in the pathogenesis of PNSAH.

Different Expression of MicroRNA-146a in Peripheral Blood CD4(+) T Cells and Lesions of Oral Lichen Planus.

Oral lichen planus (OLP) is a common T cell-mediated chronic inflammatory disease of unknown etiology. Recent increasing evidence indicates that microRNA-146a (miR-146a) plays a vital role in inflammatory diseases and T cell regulation. This study aimed to investigate the expression of miRNA-146a in peripheral blood CD4(+) T cells and local OLP lesions and to evaluate its relationship with clinical forms of OLP. Sixteen patients with OLP were divided into two groups: erosive OLP and nonerosive OLP. The expression of miR-146a was examined by quantitative real-time polymerase chain reaction. The expression of miR-146a in peripheral blood CD4(+) T cells showed no significant difference between OLP group and control group (P > 0.05), and among erosive OLP, nonerosive OLP, and control groups (P > 0.05 for all). The expression in local lesions of the OLP group was significantly higher than that of the control group (P = 0.003), and it was significantly higher in the erosive OLP group than in the non-erosive OLP (P = 0.010) and control groups (P = 0.007). However, miR-146a expression in the nonerosive OLP group did not significantly differ from that in the control group (P > 0.05). These data indicate that miR-146a might be more involved in the local immune disorder of OLP. MiR-146a might be utilized as a candidate biomarker to estimate the severity of OLP.

Heavy metal removal and crude bio-oil upgrading from Sedum plumbizincicola harvest using hydrothermal upgrading process.

The main aim of this study was to separate heavy metals and yield crude bio-oil from a heavy metals hyperaccumulator harvest, Sedum plumbizincicola, through hydrothermal upgrading process. Parameters such as granularity, temperature, pressure, and duration were examined for their effect on the removal efficiency of heavy metals and upgrading efficacy of crude bio-oil. Maximum heavy metal removal efficiency of >99% and crude bio-oil upgrading efficiency of >63% were attained with an 18 mesh (1mm) granularity, and 22.1MPa at 370 degrees C in the presence of 10mg/L additives for 60s. Under these optimized conditions, an oil phase (mostly composed of phenolic hydrocarbons and derivatives), a water phase raffinate containing Zn(2+) (0.39g/L), Pb(2+) (0.10g/L), Cu(2+) (0.16g/L), and a solid phase (the hydrothermal upgrading residue, which completely satisfies the limit set by China legislation related to biosolids disposal, were obtained).

Heavy metal removal and crude bio-oil upgrading from Sedum plumbizincicola harvest using hydrothermal upgrading process.

The main aim of this study was to separate heavy metals and yield crude bio-oil from a heavy metals hyperaccumulator harvest, Sedum plumbizincicola, through hydrothermal upgrading process. Parameters such as granularity, temperature, pressure, and duration were examined for their effect on the removal efficiency of heavy metals and upgrading efficacy of crude bio-oil. Maximum heavy metal removal efficiency of >99% and crude bio-oil upgrading efficiency of >63% were attained with an 18 mesh (1 mm) granularity, and 22.1 MPa at 370 degrees C in the presence of 10 mg/L additives for 60 s. Under these optimized conditions, an oil phase (mostly composed of phenolic hydrocarbons and derivatives), a water phase raffinate containing Zn2+ (0.39 g/L), Pb2+ (0.10 g/L), Cu2+ (0.16 g/L), and a solid phase (the hydrothermal upgrading residue, which completely satisfies the limit set by China legislation related to biosolids disposal, were obtained).

Heavy metal removal and crude bio-oil upgrade from Sedum alfredii Hance harvest using hydrothermal upgrading.

In this study, heavy metals were removed and crude bio-oil was yielded from a heavy metal hyperaccumulator harvest, Sedum alfredii Hance, through hydrothermal upgrading process. This paper reports on the optimization of process parameters for the removal of heavy metals (zinc, lead, and copper) and for the upgrading of crude bio-oil from this biomass in an autoclave. Parameters such as granularity, temperature, pressure, and duration were examined for their effect on the removal efficiency of heavy metals and upgrading efficacy of crude bio-oil. Maximum heavy metal removal efficiency of >99% and crude bio-oil upgrading efficiency of >60% were attained with an 18 mesh (1 mm) granularity, and 22.1 MPa at 370 degrees C in the presence of 10 mg/L additives (K(2)CO(3)) for 60 s. Under these optimized conditions, an oil phase (mostly composed of phenolic hydrocarbons and derivatives), a water phase raffinate (containing Zn(2+) (0.39 g/L), Pb(2+) (0.10 g/L), Cu(2+) (0.15 g/L)), and a solid phase (the hydrothermal upgrading residue, which completely satisfies the limit set by China legislation related to biosolids disposal) were obtained.