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Abstract Background A high concentration of cisplatin (CDDP) induces apoptosis in many tumor cell lines. CDDP has been administered by infusion to avoid severe toxicity. Recently, it has been reported that changes in survivin expression or function may lead to tumor sensitization to chemical and physical agents. The aim of this study was to determine whether a dominant-negative mouse survivin mutant could enhance the anti-tumor activity of CDDP. Methods A plasmid encoding the phosphorylation-defective dominant-negative mouse survivin threonine 34→alanine mutant (survivin T34A) complexed to a DOTAP-chol liposome (Lip-mS) was administered with or without CDDP in Lewis Lung Carcinoma (LLC) cells and in mice bearing LLC tumors, and the effects on apoptosis, tumor growth and angiogenesis were assessed. Data were analyzed using one-way analysis of variance(ANOVA), and a value of P < 0.05 was considered to be statistically significant. Results LLC cells treated with a combination of Lip-mS and CDDP displayed increased apoptosis compared with those treated with Lip-mS or CDDP alone. In mice bearing LLC tumors and treated with intravenous injections of Lip-mS and/or CDDP, combination treatment significantly reduced the mean tumor volume compared with either treatment alone. Moreover, the antitumor effect of Lip-mS combined with CDDP was greater than their anticipated additive effects. Conclusion These data suggest that the dominant-negative survivin mutant, survivin T34A, sensitized LLC cells to chemotherapy of CDDP. The synergistic antitumor activity of the combination treatment may in part result from an increase in the apoptosis of tumor cells, inhibition of tumor angiogenesis and induction of a tumor-protective immune response.

One of the most crucial considerations for practical applications of organic photovoltaics (OPV) is the stability under sunlight irradiation. It is necessary to translate the small device stability to the module level. Herein, the photostability of the OPV module with three cells connected in series with a total effective area of 10.8 cm2 is presented. The stability of the OPV module is studied under continuous irradiation by a UV light‐emitting diode (LED) with integrated UV intensity the same as AM1.5 solar irradiations. As a result, the OPV module achieves good stability under UV light with a half‐lifetime of about 1300 h without a UV filter. The lifetime is similar to the small device with the same materials. The series resistance and the encapsulation must be optimized simultaneously. The suitable metal of the external electrode greatly improves the OPV module's performance. In addition, the UV stability of the normal structure is shown to be better than the inverted structure because of the photoinstability of the ZnO layer. Moreover, the UV stability of semitransparent OPV modules is shown to be‐ similar to the opaque ones. [ABSTRACT FROM AUTHOR]

Studies have revealed that both extracorporeal shock‐wave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) can accelerate wound healing. This study aimed to compare the effectiveness of ESWT and HBOT in enhancing diabetic wound healing. A dorsal skin defect in a streptozotocin‐induced diabetes rodent model was used. Postoperative wound healing was assessed once every 3 days. Histologic examination was performed with hematoxylin and eosin staining. Proliferation marker protein Ki‐67 (Ki‐67), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) were evaluated with immunohistochemical (IHC) staining. The wound area was significantly reduced in the ESWT and HBOT groups compared to that in the diabetic controls. However, the wound healing time was significantly increased in the HBOT group compared to the ESWT group. Histological findings showed a statistical increase in neovascularization and suppression of the inflammatory response by both HBOT and ESWT compared to the controls. IHC staining revealed a significant increase in Ki‐67, VEGF, and eNOS but suppressed 8‐OHdG expression in the ESWT group compared to the HBOT group. ESWT facilitated diabetic wound healing more effectively than HBOT by suppressing the inflammatory response and enhancing cellular proliferation and neovascularization and tissue regeneration. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP). Methods This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for [greater than or equal to]48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter. Results The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay. Conclusion Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach., Author(s): Juan Zeng [sup.1], Chun-Ting Wang [sup.1], Fu-Shen Zhang [sup.2], Feng Qi [sup.2], Shi-Fu Wang [sup.3], Shuang Ma [sup.3], Tie-Jun Wu [sup.4], Hui Tian [sup.4], Zhao-Tao Tian [sup.5], Shu-Liu Zhang [...]

Background: Coronavirus disease 2019 (COVID‐19) impacted Hong Kong in early January 2020. Quarantine and social distancing measures have been implemented to prevent disease spread. Material and Method: Retrospective cohort study was carried out in our cluster to compare the acute appendicitis cases during pandemic period, January 1, 2020 to June 30, 2020, with the same period 1 year before. Parameters including time of presentation, complicated appendicitis rate, operative time, post‐operative complication rate, and total length of stay were compared and analysed. Results: A total number of 348 patients (160 in the pre‐COVID group versus 188 in the post‐COVID group) were included. There is no significant difference in basic demographics. The time of presentation was significantly longer in March (3.75 days vs 1.56 days, P =.031) and June 2020 (3.02 days vs 1.88 days, P =.026) compared with the pre‐COVID group, which correlate with the spike of local confirmed cases. There was a significantly higher incidence of complicated appendicitis (67% vs 52%, P =.028) and post‐operative complication rate (29% vs 7%, P =.042) in February post‐COVID group compare with the pre‐COVID group. Conclusion: During the COVID‐19 pandemic period, more patients with acute appendicitis presented late to the hospital, with an increase in complicated appendicitis rate and post‐operative complication rate. [ABSTRACT FROM AUTHOR]

Extracorporeal shockwave therapy (ESWT) has a significant positive effect to accelerate chronic wound healing. This study investigated whether the vascular endothelial growth factor (VEGF)–related pathway has involved in ESWT enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Thirty‐two male Wistar rats were divided into four groups. Group I consisted of nondiabetic control; group II, diabetic control without treatment; group III, diabetic rats received ESWT; and group IV, rats received Avastin (a VEGF monoclonal antibody) on day 0 (post‐wounding immediately) to day 7 and ESWT on day 3 and day 7. The wound healing was assessed clinically. The VEGF, endothelial nitric oxide synthase (eNOS), and Ki‐67 were analyzed with immunohistochemical staining. The mRNA expression of mitogen‐activated protein kinase–related genes was measured by real‐time quantitative real‐time polymerase chain reaction. The results revealed wound size was significantly reduced in the ESWT‐treated rats as compared to the diabetic control (p < 0.01). The positive effect of ESWT‐increasing wound healing was significantly suppressed in pretreatment of the Avastin group. Histological findings revealed significant increase in neo‐vessels in the ESWT group as compared to the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and Ki‐67 expressions were noted in the ESWT group as compared to that in controls. However, Avastin suppressed the shockwave effect and down‐regulation of VEGF, eNOS, and Ki‐67 expressions in the Avastin‐ESWT group as compared to that in the ESWT alone group. We found that highly mRNA expression of Kras, Raf1, Mek1, Jnkk, Jnk, and Jun at early stage in the ESWT group, as compared to the diabetic control. These evidences indicated treatment with multiple sessions of ESWT significantly enhanced diabetic wound healing associated with increased neovascularization and tissue regeneration. The bio‐mechanism of ESWT‐enhanced wound healing is correlated with VEGF and mitogen‐activated protein kinase–mediated pathway. [ABSTRACT FROM AUTHOR]

A blind carrier synchronization scheme based on minimum mean square error (MMSE) phase error detector and digital 2nd order loop is proposed for the demodulation of APSK in a low-SNR environment. In contrast to the existing decision-directed (DD) algorithm, which is widely adopted for blind synchronization, MMSE phase error detector does not involve the hard symbol decision mechanism, thus it is not sensitive to the false judgment of symbol. Obviously, the detection range is broadened and the degree of phase ambiguity is decreased. To reduce the computational overhead of MMSE detector, a look-up table methodology is used in the scheme. Implementation considerations concerning the key parameters of the carrier phase synchronization loop, the sample-rate adaptive strategy and the fixed point design are summarized. [ABSTRACT FROM AUTHOR]

Biot2 is a novel murine testis-specific gene that was first identified using the SEREX technique, and named by our laboratory. Using conventional RT-PCR and real time RT-PCR, we tested the expression profile of Biot2 in normal tissues and various murine tumor cell lines. Using RNA interference, we studied the biological function of Biot2 in tumorigenesis. We applied various types of growth assay, such as the in vitro MTT, colony-forming and BrdU incorporation assays, along with in vivo tumorigenicity assays, to reveal its inhibition of tumor cell proliferation. The results revealed that the Biot2 transcript was detected only and strongly in the testis tissues and abundantly in five types of murine cancer cell line. Treating B16 murine melanoma, LL/2 murine Lewis lung carcinoma and CT26 murine colorectal adenocarcinoma with special shRNA targeting Biot2 can significantly reduce the proliferation rate of these three tumor cell lines in vitro, as measured by the MTT, colony-forming and BrdU incorporation assays. The tumorigenicity of the CT26 cells transfected with special shRNA targeting Biot2 was also decreased distinctly in vivo compared with the control. It was therefore concluded that Biot2 plays a key role in tumorigenesis and could be a potential target for biotherapy. [ABSTRACT FROM AUTHOR]

Extracorporeal shock-wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio-mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin-induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW-1) on day 3 (800 impulses at 0.09 mJ/mm2) postwounding; group IV included rats that underwent two sessions of ESWT (ESW-2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW-3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT-treated rats, especially in the ESW-2 and ESW-3 groups, as compared with the control ( p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro-inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW-2 and ESW-3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo-angiogenesis and tissue regeneration, and topical anti-inflammatory response. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave (ESW) treatment has a positive effect of rescuing ischemic skin flaps. This study assessed whether ESW treatment rescues the compromised flap tissue by suppressing the apoptosis of ischemic tissue and recruiting tissue remodeling. We used a random-pattern extended dorsal–skin-flap (10 × 3 cm) rodent model. Thirty-six male Sprague–Dawley rats were divided into three groups. Group I, the control group, received no treatment. Group II received one session of ESW treatment (500 impulses at 0.15 mJ/mm2) immediately after surgery. Group III received two sessions of ESW treatment, immediately and the day after the surgery. Results indicated that the necrotic area in the flaps in group II was significantly smaller than that of the flaps in group I ( p<0.01). Transferase dUTP-nick end labeling (TUNEL) analysis revealed a significant decrease in the number of apoptotic cells in group II. Hydrogen peroxide (H2O2) expression in circulation blood was significantly decreased in group II on the day after ESW treatment. Immunohistochemical staining indicated that compared with no treatment, ESW treatment could substantially increase proliferating cell nuclear antigen (PCNA), endothelial nitric oxide synthase, and prolyl 4-hydroxylase (rPH) expression, reduce CD45 expression, and suppress 8-hydroxyguanosine (8-OG) expression in the ischemic zone of the flap tissue. In conclusion, ESW treatment administered at an optimal dosage exerts a positive effect of rescuing ischemic extended skin flaps. The mechanisms of action of ESWs involve modulation of oxygen radicals, attenuation of leukocyte infiltration, decrease in tissue apoptosis, and recruitment of skin fibroblasts, which results in increased flap tissue survival. [ABSTRACT FROM AUTHOR]

Far-infrared ray (FIR) therapy has been applied in the tissue regeneration field. Studies have revealed that FIR could enhance wound healing. However, the biological effects of FIR on diabetic wounds remain unclear. Our study aims to investigate whether FIR could accelerate diabetic wound healing and analyze the biomechanisms. A dorsal skin defect (area, 6 × 5 cm2) in a streptozotocin (STZ)-induced diabetes rodent model was designed. Thirty-two male Wistar rats were divided into 4 groups (n = 8 each subgroup). Group 1 consisted of sham, non-diabetic control; group 2, diabetic control without treatment; group 3, diabetic rats received 20 min FIR (FIR-20, 20 min per session, triplicate/weekly for 4 weeks) and group 4, diabetic rats received 40 min FIR (FIR-40, 40 min per session, triplicate in one week for 4 weeks). The wound healing was assessed clinically. Skin blood flow was measured by laser Doppler. The vascular endothelial growth factor (VEGF), 8-hydroxy-2-deoxyguanosine (8-OHdG), eNOS, and Ki-67, were analyzed with immunohistochemical (IHC) staining. Laser Doppler flowmetry analysis of the blood flow of wounding area revealed the blood flow was higher in diabetic rats who received 40 min FIR (FIR-40) as compared to that in FIR-20 group. The wounding area was significantly reduced in the FIR-40 group than in the diabetic control groups. Histological findings of peri-wounding tissue revealed a significant increase in the neo-vessels in the FIR-treated groups as compared to the controls. IHC staining of periwounding biopsy tissue showed significant increases in angiogenesis expressions (VEGF, eNOS, and EGF), cell proliferation (Ki-67), and suppressed inflammatory response and oxygen radicles (CD45, 8-OHdG) expressions in the FIR-treated groups as compared to that in controls. Treatment with the optimal dosage of FIR significantly facilitated diabetic wound healing and associated with suppressed pro-inflammatory response and increased neovascularization and tissue regeneration. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3β (GSK-3β) is involved in epithelial differentiation during wound healing. This study investigated whether the enhancement of diabetic wound healing by ESWT is associated with the GSK-3β-mediated Wnt/β-catenin signaling pathway. A dorsal skin wounding defect model using streptozotocin-induced diabetic rodents was established. Rats were divided into 4 groups: group 1, normal controls without diabetes; group 2, diabetic controls without treatment; group 3, diabetic rats receiving ESWT; and group 4, rats receiving 6-bromoindirubin-3′oxime (BIO), a GSK-3β inhibitor, to trigger Wnt/β-catenin signaling. Tissue samples were collected and analyzed by immunohistochemical (IHC) staining and quantitative RT-PCR. The ESWT and BIO-treated groups both exhibited significant promotion of wound healing compared to the healing in controls without treatment. RT-PCR analysis of Wnt-1, -3a, -4, -5a, and -10 and β-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and β-catenin levels were significantly increased in the ESWT and BIO treatment groups compared to the control groups. ESWT enhancement of diabetic wound healing is associated with modulation of the GSK-3β-mediated Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Our former studies have demonstrated that extracorporeal shock wave therapy (ESWT) could enhance diabetic wound healing but the bio-mechanisms remain elusive. This study investigated the changes of topical peri-wounding tissue expressions after ESWT in a rodent streptozotocin-induced diabetic wounding model by using the proteomic analysis and elucidated the molecular mechanism. Diabetic rats receiving ESWT, normal control, and diabetic rats receiving no therapy were analyzed. The spots of interest in proteome analysis were subjected to mass spectrometry to elucidate the peptide mass fingerprints. Protein expression was validated using immunohistochemical staining and related expression of genes were analyzed using real-time RT-PCR. The proteomic data showed a significantly higher abundance of hemopexin at day 3 of therapy but down-regulation at day 10 as compared to diabetic control. In contrast, the level of serine proteinase inhibitor (serpin) A3N expression was significantly decreased at day 3 therapy but expression was upregulated at day 10. Using real-time RT-PCR revealed that serpin-related EGFR-MAPK pathway was involved in ESWT enhanced diabetic wound healing. In summary, proteome analyses demonstrated the expression change of hemopexin and serpin with related MAPK signaling involved in ESWT-enhanced diabetic wound healing. Modulation of hemopexin and serpin related pathways are good strategies to promote wound healing. [ABSTRACT FROM AUTHOR]

Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4+CD25+ Tregs obviously reduced the suppressive activity of CD4+CD25+ Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4+CD25+ Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4+CD25+ Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4+CD25+ Tregs. Pretreated CD4+CD25+ Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4+CD25− T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4+CD25+ Tregs and might be a potential immunomodulator for the treatment of septic complications. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Previous studies have demonstrated that extracorporeal shock wave therapy (ESWT) could accelerate diabetic wound healing and that the inhibition of glycogen synthase kinase-3β (GSK-3β) is involved in epithelial differentiation during wound healing. This study investigated whether the enhancement of diabetic wound healing by ESWT is associated with the GSK-3β-mediated Wnt/β-catenin signaling pathway. A dorsal skin wounding defect model using streptozotocin-induced diabetic rodents was established. Rats were divided into 4 groups: group 1, normal controls without diabetes; group 2, diabetic controls without treatment; group 3, diabetic rats receiving ESWT; and group 4, rats receiving 6-bromoindirubin-3'oxime (BIO), a GSK-3β inhibitor, to trigger Wnt/β-catenin signaling. Tissue samples were collected and analyzed by immunohistochemical (IHC) staining and quantitative RT-PCR. The ESWT and BIO-treated groups both exhibited significant promotion of wound healing compared to the healing in controls without treatment. RT-PCR analysis of Wnt-1, -3a, -4, -5a, and -10 and β-catenin expression showed significantly increased expression in the ESWT group. The IHC staining showed that Wnt-3a and -5a and β-catenin levels were significantly increased in the ESWT and BIO treatment groups compared to the control groups. ESWT enhancement of diabetic wound healing is associated with modulation of the GSK-3β-mediated Wnt/β-catenin signaling pathway.

Background: Little is known about the long-term outcomes of severe acute respiratory distress syndrome (ARDS) patients requiring extracorporeal membrane oxygenation (ECMO). This study aimed to investigate the 1-year outcomes of these patients or patients receiving mechanical ventilation (MV) and compare their health-related quality of life (HRQoL) to the general population., Methods: Severe ARDS survivors admitted to two ICUs in China between January 2012 and January 2014 were enrolled. Of the severe ARDS survivors enrolled, 1-year postdischarge, HRQoL assessment using the Short-Form 36 (SF-36) and EuroQol questionnaire dimensions, 6-min walking distance, chest computed tomography scan, pulmonary function, and arterial blood gas analysis were compared for ARDS patients with or without ECMO., Results: ARDS patients receiving ECMO had a significantly higher Acute Physiology and Chronic Health Evaluation II score (30.3 ± 6.7 vs. 26.5 ± 7.3, P= 0.036), lung injury score (3.3 ± 0.4 vs. 2.8 ± 0.5, P= 0.000), Sequential Organ Failure Assessment score (10.8 ± 3.5 vs. 7.9 ± 3.1, P= 0.000), lower PaO2/FiO2ratio ([mmHg, 1 mmHg = 0.133 kPa], 68.3 ± 16.1 vs. 84.8 ± 16.5, P= 0.000), and increased extrapulmonary organ failure (2 [1, 3] vs. 1 [1, 1], P= 0.025) compared with patients not receiving ECMO. ECMO and non-ECMO survivors showed similar pulmonary function, morphological abnormalities, resting arterial blood gas values, and 6-min walking distance. Mild pulmonary dysfunction and abnormal morphology were observed in a few survivors. In addition, ECMO and non-ECMO survivors showed a similar quality of life. ECMO survivors showed lower SF-36 physical functioning and role-physical domain scores (minimum clinically significant difference at least 5 points), and non-ECMO survivors had similar outcome., Conclusions: One-year posthospital discharge, severe ARDS survivors receiving ECMO or MV demonstrated comparable outcomes. Compared with the general population, ARDS survivors showed reduced HRQoL. Pulmonary function and lung morphology revealed sufficient recovery with minor lung impairment.

Naturally occurring CD4 + CD25 + regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4 + CD25 + Tregs obviously reduced the suppressive activity of CD4 + CD25 + Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4 + CD25 + Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4 + CD25 + Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4 + CD25 + Tregs. Pretreated CD4 + CD25 + Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4 + CD25 - T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4 + CD25 + Tregs and might be a potential immunomodulator for the treatment of septic complications.

Cancer cells activate autophagy in response to anticancer therapies. Autophagy induction is a promising therapeutic approach to treat cancer. In a previous study, YL4073 inhibited the growth of liver cancer and induced liver cancer cell apoptosis. Here, we demonstrated the anticancer activity and specific mechanisms of YL4073 in Lewis lung carcinoma LL/2 cells. Our results show that YL4073-induced autophagy was followed by apoptotic cell death. The anticancer and autophagy stimulating efficacy was confirmed by several factors, including the appearance of autophagic vacuoles, formation of acidic vesicular organelles, recruitment of microtubule-associated protein 1 light chain 3 II (LC3-II) to the autophagosomes, conversion and cleavage of LC3-I to LC3-II, upregulation of Beclin 1 expression, and formation of the Atg12-Atg5 conjugate in LL/2 cells after YL4073 treatment for 24 or 48 h. Furthermore, P53 activation and p-histone H3 phosphorylation occurred after cell exposure to YL4073 for 48 h, suggesting that cell apoptosis had occurred. Pharmacological inhibition of autophagy using 3-methyladenine increased cell apoptosis. Molecular level studies revealed that YL4073 inhibited survival signalling by blocking the activation of Akt and mTOR phosphorylation and reduced the expression of p-mTOR downstream targets for phosphorylation, including p70S6K, p-TSC, p-MAPK, and p-AMPK. This suggests that the Akt/mTOR/p70S6K and TSC/MAPK/AMPK pathways are involved in the effects of YL4073 treatment in LL/2 cells. In addition, YL4073 significantly inhibited LL/2 tumor growth and induced apoptosis in vivo. These data suggest that YL4073 has a significant anticancer effect, with a pathway-specific mechanism of autophagy both in vitro and in vivo.

Cell-based therapy is an attractive approach for the treatment of chronic nonhealing wounds. This study investigated whether adipose-derived stem cells (ASCs) can accelerate diabetic wound healing and traffic in the engraftment of ASCs. Dorsal full-thickness skin wound defects (6 × 5 cm) were created in a streptozotocin (STZ)-induced diabetes rodent model. Group I served as a nondiabetic normal control, group II served as a diabetic control without ASCs, and group III included rats that were injected subcutaneously in the wound margin twice with nondiabetic ASCs (1 × 10(7) ASCs/dose). The wound healing was assessed clinically. Histological examination and immunohistochemical analyses of periwound tissue were performed. Green fluorescence protein (GFP)(+)-ASCs were used to examine the engraftment of these cells after injection. XenoLight DiR-labeled ASCs were implanted to detect migration ability using an IVIS imaging system. Results revealed that complete wound healing time statistically decreased in the ASC-treated group compared to the controls (p < 0.001). Histological examination revealed the ASC-treated group showed a significant reduction in the proinflammatory reaction, with significantly increased levels of EGF, VEGF, rPH, and Ki-67 expression compared to the controls. The populations of GFP(+)-ASCs in circulating blood significantly increased after ASC injection compared to those of controls. Immunofluorescence staining showed GFP(+)-ASCs significantly accumulated in the subdermal layer of the wound margin and increased angiogenesis via vWF and VEGF expression after injection. IVIS analysis revealed ASCs could exist and home into the periwound area up to 8 weeks postimplantation. In conclusion, ASCs significantly enhanced diabetic wound healing, engrafted into the local wound tissue, and implanted into circulating blood. ASC treatment stimulated neoangiogenesis and increased tissue regeneration through paracrine and autocrine mechanisms.

Objective: To investigate the expression of high mobility group protein B1 (HMGB1) and its receptor, receptor for advanced glycation end-product (RAGE), in renal cancer tissue and surrounding normal tissue and to analyze the relationship between the expression level of the protein and receptor as well as the clinical pathological characteristics and prognosis in renal cancer patients., Methods: A total of 80 renal carcinoma patients who were surgically treated in our hospital from February 2004 to December 2012 were included in this study. Normal paratumoral tissues were collected as a control. All diagnoses were confirmed with a postoperative pathological examination. All patients had complete pathological data. The expression of HMGB1/RAGE proteins in renal cancer tissue and paratumoral tissue was examined using immunohistochemical methods., Results: The positive expression rate of HMGB1 was 71% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (25%). The positive expression rate of RAGE was 72% in renal cancer tissue, which was significantly higher than that in the paratumoral normal tissue (27%). Further analysis did not indicate a correlation between the positive expression of HMGB1 and RAGE proteins and gender, age and tumor size (P > 0.05), whereas the expression patterns were shown to correlate with tumor differentiation, clinical stage and lymph node metastasis (P < 0.05). The expression of HMGB1 exhibited a significant positive correlation with RAGE level (P < 0.05), the expression of HMGB1/RAGE proteins exhibited a negative correlation with the prognosis of patients, and the five-year survival rate of patients with positive expression was significantly lower than that of patients with negative expression (P < 0.05)., Conclusion: HMGB1/RAGE exhibited significantly elevated expression in renal cancer tissues that was closely related to the clinical prognosis of patients; thus, the expression levels may become a new target in the treatment of renal carcinoma.

Biot2 is a tumor-associated antigen, and it is a novel gene (GenBank EF100607) that was first identified with the SEREX technique and named by our laboratory. It is highly expressed in cancer cells and testis, with low or no expression in normal tissues. In our previous study, RNA interference of human Biot2 can inhibit tumor cell growth, and it is associated with poor prognosis of patients in clinical study; however, the mechanism of Biot2 that effects tumor growth is not yet clear. Here, in this study, we explore further the mechanism of Biot2 by silencing Biot2 in CT26 cells. It provides some theoretical basis for Biot2 as a new target for gene therapy. In CT26 cells, the expression of Biot2 was downregulated by Biot2-shRNA. It also promoted G1 phase arrest, the expression of p16 and p21, and cell apoptosis. In the mouse model, the tumor volume and the expression of PCNA of the Biot2-shRNA group significantly decreased. These results suggest that silencing Biot2 in CT26 cells by RNA interference can inhibit cell growth in vitro and in vivo. It also induces cell cycle arrest in the G1 phase and apoptosis throughout regulation of p16 and p21. Taken together, our data demonstrate that Biot2 can be a potential target of gene therapy.

Objective: This study aims to identify morphological changes in the lung parenchyma of acute respiratory distress syndrome (ARDS) survivors after extracorporeal membrane oxygenation  (ECMO) by high-resolution computed tomography (HRCT) follow-up. Factors influencing these changes are also examined., Methods: Information and lung HRCT scans were collected and studied 1, 3, 6, and 12 months after the withdrawal of severe ARDS survivors rescued by ECMO in the Respiratory Care Unit of Beijing Chaoyang Hospital from November 2009 to August 2012. The observation endpoint was set as the time when the lung lesions were basically absorbed or 12 months after withdrawal., Results: Among nine survivors, one survivor was lost to follow-up. The lesions of two patients, which were attributed to bacterial pneumonia and pneumocystis pneumonia, were basically absorbed 1 month after surgery. Six patients completed the 12 month follow-up. Although initial morphological changes varied, different degrees of absorption improvement were observed in later stages of treatment. Lung HRCT analysis on the sixth month indicated that the degree of involvement of the ventral region was greater than that of the dorsal area. No significant difference was observed in patients in terms of ECMO support time, pre-ECMO Murray score, and APACHE II score, among others., Conclusion: Lung HRCT of severe ARDS survivors after ECMO treatment showed various degrees of morphological changes in the lung parenchyma. The severity of these changes may be associated with the disease duration.

Pemetrexed is an antifolate agent which has been used for treating malignant pleural mesothelioma and non small lung cancer in the clinic as a chemotherapeutic agent. In this study, pemetrexed inhibited cell growth and induced G1 phase arrest in the A549 cell line. To explore the molecular mechanisms of pemetrexed involved in cell growth, we used a two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics approach to analyze proteins changed in A549 cells treated with pemetrexed. As a result, twenty differentially expressed proteins were identified by ESI-Q-TOF MS/MS analysis in A549 cells incubated with pemetrexed compared with non-treated A549 cells. Three key proteins (GAPDH, HSPB1 and EIF4E) changed in pemetrexed treated A549 cells were validated by Western blotting. Accumulation of GAPDH and decrease of HSPB1 and EIF4E which induce apoptosis through inhibiting phosphorylation of Akt were noted. Expression of p-Akt in A549 cells treated with pemetrexed was reduced. Thus, pemetrexed induced apoptosis in A549 cells through inhibiting the Akt pathway.

Background: Vascular endothelial growth factor (VEGF)-D has been shown to promote lymph node metastasis in several cancers. Although generally overexpressed in ovarian carcinoma, its role in nodal dissemination of this cancer is unclear. To clarify the role of VEGF-D and the underlying molecular mechanisms, we investigated the function of VEGF-D using a mouse xenograft model of ovarian cancer., Methods: Human ovarian serous adenocarcinoma SKOV3 cells were transfected with VEGF-D recombinant plasmid DNA, or with control vectors. The cells were injected subcutaneously into the footpads of nude mice. Tumor growth was evaluated weekly. Draining lymphatics were observed grossly with Evan's blue lymphangiography. Tumoral lymphatics were delineated with both Evan's blue and LYVE-1 immunostaining. Tumor metastases to lymph nodes were evaluated by H&E and CA125/CD40 staining. Expression of VEGF-D in primary tumors and levels of CA125 in involved lymph nodes were examined by immunohistochemistry. Tumor cell apoptosis was analyzed by Hoechst dyeing., Results: Mice bearing VEGF-D overexpressing xenografts showed a significantly higher rate of lymph node metastasis and markedly greater tumor volume compared with the controls. The functional lymphatic vessels were denser and enlarged in marginal and central tumor portions. Additionally, higher CA125 expression was observed in the involved lymph nodes. Mice bearing VEGF-D overexpressing xenografts also exhibited a markedly lower apoptotic index compared with the controls., Conclusions: Our data demonstrate the important role of VEGF-D in promoting lymph node metastasis by increasing tumor lymphangiogenesis, stimulating draining lymphatic vessel formation, and enhancing tumor invasiveness. Our findings show that VEGF-D can be a promising therapeutic target for ovarian cancer.