Growth responses to irradiance regime along an ecological gradient of <Emphasis Type="Italic">Quercus</Emphasis> <Emphasis Type="Italic">castaneifolia</Emphasis> seedlings of different provenance

Understory light is known as one of the most important environmental predictors of growth response of woody species. Hence, the primary objective of most forest management practices is optimizing that resource for understory seedlings. In this study, growth responses of Quercus castaneifolia seedlings from five different provenances from west to east of the Hyrcanian forest were investigated along their ecological gradients (from high to low precipitation). An experimental design was executed under controlled conditions at eight different irradiance levels (10, 20, 30, 40, 50, 60, 70 and 100 % full irradiance). Results showed that the irradiance is probably the most important determinant of variation in seedling characteristics. Among all investigated variables, variability in seedling size was affected significantly by provenance, while seedling morphology and their architectural response was affected by different levels of irradiance in a curvilinear manner. The biggest changes were observed at lowest irradiance levels (10–20 %) while at higher irradiance (70–100 %) the curves flatten. It was shown that, unlike at low irradiance levels, there is little capacity in seedling morphology to acclimatize with high irradiance intensity. Attaining maximal biomass varies across provenances and irradiance gradient. The highest biomass for the five provenances could be ranked as follows: 20–60 % and 50–60 % for the wetter and drier provenances, respectively. These results demonstrated that the light requirement increases from wetter to drier provenances, with a negative relationship between light requirement and precipitation regime. Different responses to irradiance levels may be the result of genetic adaptation to the ecological conditions prevailing in native habitat, especially precipitation regime.     

Binding of divalent metal ions to calcium-free peroxidase: thermodynamic and kinetic studies

Thermodynamics of binding of divalent metal ions including Ca(2+) , Mg(2+) , Ba(2+) , and Cd(2+) to Ca-free horseradish peroxidase (HRP) enzyme was investigated using UV/VIS spectrophotometry and molecular-mechanic (MM) calculations. According to the obtained binding and thermodynamic parameters, trend of the relative binding affinities of these divalent metal cations was found to be: Ca(2+) >Cd(2+) >Mg(2+) >Ba(2+) . Binding analysis based on Scatchard and Hill models showed positive cooperativity effect between the two distal and proximal binding sites. Furthermore, kinetics of binding and reconstitution process was examined (using relaxation-time method) for binding of Ca(2+) (as the typical metal ion) to Ca-free HRP, which was found a second-order type having a two-step mechanism involving fast formation of Ca-free HRP/1?Ca(2+) as the kinetic intermediate in step 1. Finally, by means of MM calculations, the comparative stability energies were evaluated for binding of M(2+) metal cations to Ca-free HRP. Based on MM calculations, preferential binding of Ca(2+) ion was occurred on distal and proximal binding sites of Ca-free HRP associated with higher stability energies (E(total) ). Indeed, among the divalent metal ions, Ca(2+) with the highest binding affinity (maximum value of K(bin) and minimum value of ΔG$\rm{{_{bin}^{0}}}$), maximum value of exothermic binding enthalpy, and stability energies stabilizes the HRP structure along with an optimized catalytic activity.     

Association of Mycobacterium infections in patients with Mendelian susceptibility to mycobacterial disease with venous thromboembolism

An association between a hypercoagulable state and Mendelian susceptibility to mycobacterial disease (MSMD) has been established in a few studies; resultant thrombosis is considered rare. In a case‐control study, the prevalence of factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C mutations were investigated in mycobacterium‐infected patients. The study comprised 30 patients with mycobacterial infections (invasive, disseminated and/or recurrent infections with Bacille Calmette–Guerin or non‐tuberculosis mycobacteria and Mycobacterium Tuberculosis with positive results for acid‐fast bacilli and tuberculin skin tests) and 30 normal healthy controls. Forty female (66.7%) and 20 male subjects (33.3%) aged from 3 to 70 years were recruited into this study. Genotyping of targeted genes was performed by RT‐PCR and cytokine TNF‐α concentrations were quantified using a commercially available ELISA kit. Significant associations between mycobacterial infection and TNF‐α production after stimulating peripheral blood mononuclear cells with LPS alone and with IFN‐γ plus LPS were identified. Moreover, genotyping analysis in the studied population revealed a significant association between MTHFR c.677C>T (OR, 3.28; 95% CI, 1.35–7.92; P < 0.05), MTHFR c.1298A>C (OR, 2.33; 95% CI, 1.10–4.93; P < 0.05) and mycobacterial infection in affected patients, indicating susceptibility to venous thromboembolism according to previous studies. Additionally, mycobacterium‐infected patients had a significantly greater prevalence of MTHFR C677T and A1298C mutations than controls.     

Association and impact of <Emphasis Type="Italic">XPG Asp</Emphasis> 1104 <Emphasis Type="Italic">His</Emphasis> gene polymorphism in HIV 1 disease progression to AIDS among north Indian HIV seropositive individuals

Various efforts made to stop the deadly epidemic of HIV since its discovery in 1983 remain unsuccessful and this virus still continues to claim the lives of millions of individuals every year. The viral effect in the cell is complicated and the overall disease outcome is the result of interaction between a few viral proteins and complex host immune response. Because it has been reported that XPG (Xeroderma pigementesum group G) gene does play a role in reducing UV induced apoptosis and participate in Nucleotide Excision Repair (NER) process of DNA damage, it was hypothesized that polymorphism in this gene may have a role in HIV 1 disease progression to AIDS. The aim of the present study, therefore, was to find out the association between XPG gene polymorphism and its effect on the rate of HIV 1 disease progression to AIDS. 300 HIV seropositive cases and an equal number of age and sex matched controls were recruited for the study from north Indian population. The PCR-RFLP method was utilized to genotype 600 study subject for the XPG Asp ¹¹⁰⁴ His gene polymorphism. There was significant difference in the frequency of the His/His variant genotype (OR 1.95, 95% CI = 1.93–3.63, P = 0.04) between cases and controls indicating a probable role of this gene in host viral interactions.     

新烟碱类杀虫剂对麦扁盾蝽若虫和成虫的毒效（英文）

在伊朗, 麦扁盾蝽Eurygaster integriceps是小麦和大麦上的主要害虫。新烟碱类杀虫剂是一类具有较强活性的杀虫剂, 对刺吸式口器害虫具有良好的效果。本研究应用触杀和熏蒸两种生测方法测定了4种新烟碱类杀虫剂（噻虫嗪、吡虫啉、呋虫胺和啶虫咪）对麦扁盾蝽3龄若虫和成虫的毒效。触杀法生测结果显示, 各杀虫剂对麦扁盾蝽没有强烈的触杀活性, 但是在高浓度下（5 000 mg/L a. i.）, 可见较高的死亡率。熏蒸法生测结果显示, 所有杀虫剂对麦扁盾蝽的若虫和成虫均有较好的毒性。结果提示应用熏蒸方法可能是治理这一重要害虫的新方法。     

MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the potent antigenic targets for CAR T cell therapy of gastric adenocarcinoma

Gastric adenocarcinoma is usually diagnosed in late stages, necessitating the use of different therapeutic modalities. Currently, antibody-based therapies have also been approved through with limited clinical efficacy. Reinforcing antibody-based immunotherapy by using chimeric antigen receptor (CAR) T cells may enhance the approach. However, the cells can cause severe on-target and off-tumor toxicities owing to their higher sensitivity to low-level antigen expressions. To address the need for safe and reliable targets, we made a bioinformatics pipeline by which we screened overexpressed genes in the disease for off-tumor sites in many normal tissues. Our inspection showed that MSLN (Mesothelin), ANTXR1 (TEM8), and MUC3A are the probable targets of CAR T cell therapy in gastric adenocarcinoma. The proposed antigenic targets might respond to the need to simultaneously target multiple antigens in a tumor matrix to prevent resistance.     

Stem cell therapy: A novel approach for myocardial infarction

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Until recently, it was thought that myocardium was not able to repair itself, but studies have now shown that resident cardiac stem cells have regenerative capacity, and stem cell therapy may be a novel approach for cardiac muscle repair and regeneration. Stem cell-derived paracrine factors have been shown to regulate ventricular remodeling, inflammation, apoptosis, cardiomyocytes regeneration, and neovascularization in regions of infarcted cardiac tissue. In this review, we summarize the evidence from cellular, animal, and clinical studies supporting the potential clinical significance of stem cell therapy as a novel therapeutic approach for the treatment of MI.     

PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway

The Wnt/β-catenin pathway is one of the most common pathways dysregulated in breast cancer, and may, therefore, be a potential-therapeutic target. We have investigated the effects of PNU-74654 in breast cancer, as a Wnt/β-catenin inhibitor, either alone or in combination with fluorouracil (5-FU). PNU-74654 suppressed cell growth at an IC ₅₀ of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, our data showed that this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU. These data show the ability of PNU-74654 to specifically target Wnt pathway, interfere with cell proliferation, induce-apoptosis, reduce-migration, and synergistically interact with 5-FU, supporting further studies on this novel therapeutic-approach for breast cancer.     

Association between serum cell adhesion molecules with hs-CRP,uric acid and VEGF genetic polymorphisms in subjects with metabolic syndrome

Molecular Biology Reports - Metabolic syndrome (MetS) is associated with a pro-inflammatory state and endothelial dysfunction that places subjects with MetS at a higher risk of atherosclerosis....     

Study of quercetin and fisetin synergistic effect on breast cancer and potentially involved signaling pathways

Naturally-derived drugs have drawn much attention in recent decades. Efficiency, lower toxicity, and economic reasons are some of their advantages that justify this broad range of administration for different diseases, including cancer. If we can find a specific combination that boosts the effects of their single therapy, leading to synergism effect, increased efficiency, and decreased toxicity, they can act even better. Quercetin and fisetin, two well-known flavonoids, have been used to fight against various cancers. In this study, we investigated their possible synergism quercetin and fisetin on MCF7, MDA-MB-231, BT549, T47D, and 4T1 breast cancer cell lines. Then the optimum combined dose was used to study their impacts on wound healing abilities and clonogenic properties. The real-time qPCR was used to study the expression of their validated downstream effectors in predicted pathways. A significant synergism effect (p < .01, combination index: <1) was observed for all cell lines. Combination therapy was significantly more effective in colony formation (p < .0001) and wound healing assays (p < .001) compared to single therapies. The expression level of potential effectors was also showed a greater change. In vivo study confirmed the in vitro results and showed how significantly (p < .001) their synergism promotes their singular function in inhibiting cancer progression. The breast cancer mouse models receiving combined therapy lived longer with higher average body weight and smaller tumor sizes. These results exhibit that quercetin and fisetin inhibit cancer cell proliferation, migration and colony formation synergistically, and matrix metalloproteinase signaling and apoptotic pathways are relatively responsible for inhibitory activities.