Efficacy of Photodynamic Therapy for the Treatment of Bowen's Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Photodynamic therapy is an established treatment option for Bowen's disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO2 laser or plum-blossom needle) for the treatment of Bowen's disease. METHODS: Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration's risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. RESULTS: Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], I2 = 86%, p = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], I2 = 0%, p = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], I2 = 0%, p = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO2 laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], I2 = 0%, p < 0.0001). Photodynamic therapy combined with ablative fractional CO2 laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], I2 = 0%, p = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], I2 = 0%, p = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO2 laser and photodynamic therapy combined with ablative fractional CO2 laser (RR = 1.00, 95% CI [0.54, 1.86], I2 not applicable, p = 1.00). CONCLUSIONS: This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen's disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO2 laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen's disease warrants further exploration.

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

[Effects of cultivation patterns on wheat yield and soil fertility in dryland]. / æ ½åŸ¹æ¨¡å¼å¯¹æ—±åœ°å°éº¦äº§é‡å’ŒåœŸå£¤è‚¥åŠ›çš„å½±å“.

A field experiment was conducted to examine the effects of plastic film mulching (PM), straw retention (SR), and planting green manure (GM) on winter wheat grain yield and soil fertility. The results showed that PM did not have consistently positive effect on the grain yield, when compared to the traditional patterns (TP). No difference of average grain yield was observed between them over three years. Soil total nitrogen (N), available phosphorus (P), potassium (K), sulfur (S), zinc (Zn) and manganese (Mn) were decreased in 20-40 cm layer in PM than those in TP, while no difference was observed for soil organic matter, nitrate (NO3--N), available iron (Fe) and copper (Cu). The mean grain yield of three years decreased by 12.1% in SR than that in TP treatment. At maturity stage of winter wheat, soil total N and available Cu was increased by 5.8% in 0-20 cm and 6.2% in 20-40 cm layer, respectively, while soil available P and Mn were decreased by 36.1% and 10.2%, respectively. No difference was observed between SR and TP treatments for soil organic matter, NO3--N, available K, S, Zn and Fe at anthesis and maturity stages. Compared to the TP treatment, the mean grain yield was decreased by 12.1% in GM treatment. Soil pH, available P and S were decreased, while the soil organic matter, total N, NO3--N, and available Zn and Mn were increased. No difference was observed for soil available K, Fe and Cu. In conclusion, the PM and SR were not beneficial for the improvement of soil fertility, and thus inhibited the grain yield increase in dryland with low soil fertility level. The GM has greater potential to increase soil nutrients, but it should be paid more attention to the risk of grain yield reduction due to insufficient annual precipitation.

[Effects of cultivation patterns on wheat yield and grain nutrient concentration in dryland]. / æ ½åŸ¹æ¨¡å¼å¯¹æ—±åœ°å°éº¦äº§é‡å’Œç±½ç²’å »åˆ†å«é‡çš„å½±å“.

A field experiment was conducted to examine the effects of plastic film mulching (PM), straw retention (SR) and planting green manure (GM) on grain yield and nutrient concentrations of winter wheat. Compared to the traditional pattern (TP), plastic film mulching showed no significant effect on the average yield over the three years but increased the average phosphorus (P) uptake and concentration in grain by 8.4% and 13.0%, respectively. The average uptake of nitrogen (N), sulfur (S) and iron (Fe) was decreased by 12.6%, 15.0% and 11.1%, and the corresponding concentration was decreased by 12.1%, 12.9% and 10.1%, respectively. There was no significant effect on grain zinc (Zn) concentration. Straw retention decreased grain yield by 12.1%, reduced the average uptake of N, S and Fe decreased by 22.5%, 21.0% and 19.8%, and their corresponding concentration by 10.1%, 9.4% and 3.8%, respectively. The average uptake of P in grain was decreased by 9.8% with straw retention, while the P concentration was increased by 5.0%. There was no significant effect of straw retention on Zn concentration in grain. Planting green manure decreased the grain yield by 12.1%. It had no significant effect on the average uptake of N and Zn, but increased the grain N and Zn concentration by 12.1% and 12.6%, respectively. It showed no impact on P, S and Fe concentration in grain. The discordance between variation of grain yield and its nutrient uptake under different cultivations was the key reason for the changes of their nutrient concentration. Considering the potential adverse effects of plastic film mulching and straw retention on the quantity and quality of grain yield, suitable N fertilization should be applied to ensure the nutrient requirement for grain yield and regulate the uptake and utilization of N, S and Fe for improving the grain quality. Planting green manure could improve soil fertility and increase grain N and Zn concentration, but the yield reduction deserves more attention.

The potato sucrose transporter StSUT1 interacts with a DRM-associated protein disulfide isomerase.

Organization of proteins into complexes is crucial for many cellular functions. Recently, the SUT1 protein was shown to form homodimeric complexes, to be associated with lipid raft-like microdomains in yeast as well as in plants and to undergo endocytosis in response to brefeldin A. We therefore aimed to identify SUT1-interacting proteins that might be involved in dimerization, endocytosis, or targeting of SUT1 to raft-like microdomains. Therefore, we identified potato membrane proteins, which are associated with the detergent-resistant membrane (DRM) fraction. Among the proteins identified, we clearly confirmed StSUT1 as part of DRM in potato source leaves. We used the yeast two-hybrid split ubiquitin system (SUS) to systematically screen for interaction between the sucrose transporter StSUT1 and other membrane-associated or soluble proteins in vivo. The SUS screen was followed by immunoprecipitation using affinity-purified StSUT1-specific peptide antibodies and mass spectrometric analysis of co-precipitated proteins. A large overlap was observed between the StSUT1-interacting proteins identified in the co-immunoprecipitation and the detergent-resistant membrane fraction. One of the SUT1-interacting proteins, a protein disulfide isomerase (PDI), interacts also with other sucrose transporter proteins. A potential role of the PDI as escort protein is discussed.

Recycling of Solanum sucrose transporters expressed in yeast, tobacco, and in mature phloem sieve elements.

The plant sucrose transporter SUT1 (from Solanum tuberosum, S. lycopersicum, or Zea mays) exhibits redox-dependent dimerization and targeting if heterologously expressed in S. cerevisiae (Krügel et al., 2008). It was also shown that SUT1 is present in motile vesicles when expressed in tobacco cells and that its targeting to the plasma membrane is reversible. StSUT1 is internalized in the presence of brefeldin A (BFA) in yeast, plant cells, and in mature sieve elements as confirmed by immunolocalization. These results were confirmed here and the dynamics of intracellular SUT1 localization were further elucidated. Inhibitor studies revealed that vesicle movement of SUT1 is actin-dependent. BFA-mediated effects might indicate that anterograde vesicle movement is possible even in mature sieve elements, and could involve components of the cytoskeleton that were previously thought to be absent in SEs. Our results are in contradiction to this old dogma of plant physiology and the potential of mature sieve elements should therefore be re-evaluated. In addition, SUT1 internalization was found to be dependent on the plasma membrane lipid composition. SUT1 belongs to the detergent-resistant membrane (DRM) fraction in planta and is targeted to membrane raft-like microdomains when expressed in yeast (Krügel et al., 2008). Here, SUT1-GFP expression in different yeast mutants, which were unable to perform endocytosis and/or raft formation, revealed a strong link between SUT1 raft localization, the sterol composition and membrane potential of the yeast plasma membrane, and the capacity of the SUT1 protein to be internalized by endocytosis. The results provide new insight into the regulation of sucrose transport and the mechanism of endocytosis in plant cells.

Restoration in vitro of impaired T-cell responses in patients with chronic hepatitis B by autologous dendritic cells loaded with hepatitis B virus proteins (R2).

BACKGROUND: The purpose of the present paper was to investigate dendritic cell (DC) and T-cell functions in patients with chronic hepatitis B (CHB) and determine whether therapeutic DC vaccines could restore T-cell function in those patients in vitro. METHODS: Twelve patients with CHB and 10 normal control subjects with positivity for antibodies to hepatitis B surface and core antigens (anti-HBs and anti-HBc positivity) were enrolled in the present study. Phenotype analysis and allogeneic mixed lymphocyte reaction assay of DC from CHB patients and normal controls were made in the absence or presence of a cocktail of cytokines: interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), IL-6 and tumor necrosis factor-alpha (TNF-alpha). Autologous T-cell proliferation assays and the enzyme-linked immunospot (ELISPOT) method for detecting interferon-gamma (IFN-gamma)-producing CD8(+) T cells were used to evaluate the efficacy of DC loaded in vitro with HBsAg or HBcAg. RESULTS: The DC from CHB patients had a lower expression of costimulatory molecules CD80, CD86 and impaired allogeneic mixed lymphocyte reaction capacity compared to those from normal controls. However, the impaired DC function could be restored partially by cytokine cocktail supplemented in vitro. Mature DC loaded with HBsAg or HBcAg showed a greater capacity for autologous T-cell proliferation and antigen-specific IFN-gamma production than immature DC. Moreover, as a DC -loading antigen, HBcAg was more immunogenic than HBsAg. CONCLUSIONS: The impaired function of DC in patients with CHB may be restored by supplementation in vitro with a cocktail of cytokines, and therapeutic DC vaccines might be effective to treat CHB infection in humans.

Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences.

Early in infection, human immunodeficiency virus type 1 (HIV-1) generally uses the CCR5 chemokine receptor (along with CD4) for cellular entry. In many HIV-1-infected individuals, viral genotypic changes arise that allow the virus to use CXCR4 (either in addition to CCR5 or alone) as an entry coreceptor. This switch has been associated with an acceleration of both CD3(+) T-cell decline and progression to AIDS. While it is well known that the V3 loop of gp120 largely determines coreceptor usage and that positively charged residues in V3 play an important role, the process of genetic change in V3 leading to altered coreceptor usage is not well understood. Further, the methods for biological phenotyping of virus for research or clinical purposes are laborious, depend on sample availability, and present biosafety concerns, so reliable methods for sequence-based "virtual phenotyping" are desirable. We introduce a simple bioinformatic method of scoring V3 amino acid sequences that reliably predicts CXCR4 usage (sensitivity, 84%; specificity, 96%). This score (as determined on the basis of position-specific scoring matrices [PSSM]) can be interpreted as revealing a propensity to use CXCR4 as follows: known R5 viruses had low scores, R5X4 viruses had intermediate scores, and X4 viruses had high scores. Application of the PSSM scoring method to reconstructed virus phylogenies of 11 longitudinally sampled individuals revealed that the development of X4 viruses was generally gradual and involved the accumulation of multiple amino acid changes in V3. We found that X4 viruses were lost in two ways: by the dying off of an established X4 lineage or by mutation back to low-scoring V3 loops.