Helicobacter pylori infection reduces the efficacy of cancer immunotherapy: A systematic review and meta-analysis.

BACKGROUND: Cancer immunotherapy has shown promising results in several tumors, but its efficacy is influenced by the immune state of the body. Helicobacter pylori (H. pylori) infection can modulate the immune function of the body through various pathways, ultimately affecting the effectiveness of cancer immunotherapy. AIM: In this meta-analysis, we aimed to explore the association between H. pylori infection and the efficacy of cancer immunotherapy. METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant articles. We extracted and pooled the hazard ratio (HR) of the overall survival (OS) and progression-free survival (PFS) by Review Manager 5.4. RESULTS: Our analysis included four studies with a total of 263 participants. Compared to the control group, patients receiving cancer immunotherapy with H. pylori infection had a shorter OS (HR = 2.68, 95% CI: 2.00-4.11, p < 0.00001) and PFS (HR = 2.25, 95% CI: 1.66-3.60, p < 0.00001). CONCLUSION: Our meta-analysis suggested that H. pylori infection has a detrimental effect on cancer immunotherapy.

Remediation of Cd-Contaminated Soil by Modified Nanoscale Zero-Valent Iron: Role of Plant Root Exudates and Inner Mechanisms.

In this study, the role of exogenous root exudates and microorganisms was investigated in the application of modified nanoscale zero-valent iron (nZVI) for the remediation of cadmium (Cd)-contaminated soil. In this experiment, citric acid (CA) was used to simulate root exudates, which were then added to water and soil to simulate the pore water and rhizosphere environment. In detail, the experiment in water demonstrated that low concentration of CA facilitated Cd removal by nZVI, while the high concentration achieved the opposite. Among them, CA can promote the adsorption of Cd not only by direct complexation with heavy metal ions, but also by indirect effect to promote the production of iron hydroxyl oxides which has excellent heavy metal adsorption properties. Additionally, the H+ dissociated from CA posed a great influence on Cd removal. The situation in soil was similar to that in water, where low concentrations of CA contributed to the immobilization of Cd by nZVI, while high concentrations promoted the desorption of Cd and the generation of CA-Cd complexes which facilitated the uptake of Cd by plants. As the reaction progressed, the soil pH and cation exchange capacity (CEC) increased, while organic matter (OM) decreased. Meanwhile, the soil microbial community structure and diversity were investigated by high-throughput sequencing after incubation with CA and nZVI. It was found that a high concentration of CA was not conducive to the growth of microorganisms, while CMC had the effect of alleviating the biological toxicity of nZVI.

Molecular targeted treatment and drug delivery system for gastric cancer.

Gastric cancer is still a major cancer worldwide. The early diagnosis rate of gastric cancer in most high incidence countries is low. At present, the overall treatment effect of gastric cancer is poor, and the median overall survival remains low. Most of the patients with gastric cancer are in an advanced stage when diagnosed, and drug treatment has become the main means. Thus, new targeted drugs and therapeutic strategies are the hope of improving the therapeutic effect of gastric cancer. In this review, we summarize the new methods and advances of targeted therapy for gastric cancer, including novel molecular targeted therapeutic agents and drug delivery systems, with a major focus on the development of drug delivery systems (drug carriers and targeting peptides). Elaborating these new methods and advances will contribute to the management of gastric cancer.

Nanoscale zerovalent iron, carbon nanotubes and biochar facilitated the phytoremediation of cadmium contaminated sediments by changing cadmium fractions, sediments properties and bacterial community structure.

Environment functional materials have been widely used, but whether their effects on the contaminated environment could facilitate phytoremediation is not yet well understood. In this study, starch stabilized nanoscale zerovalent iron (SN), multiwall carbon nanotubes (MW) and tea waste derived biochar (TB) were used to facilitate the phytoremediation of cadmium (Cd) contaminated sediments by Boehmeria nivea (L.) Gaudich. Results showed that 100 mg/kg SN, 500 mg/kg MW and 500 mg/kg TB facilitated phytoremediation, as evidenced by increasing Cd accumulation and/or promoting plant growth. These concentrations of materials increased the reducible fraction of Cd by 9-10% and decreased the oxidizable proportion of Cd by 48-52%, indicating the improvement of Cd bioavailability through converting the oxidizable Cd into reducible form. The activities of urease, phosphatase and catalase, which related to nutrient utilization and oxidative stress alleviation, increased by 20-24%, 25-26%, and 8-9% in the sediments treated with 500 mg/kg MW and 500 mg/kg TB, respectively. In addition, the 16S rRNA gene sequence results showed that these concentrations of materials changed the bacterial diversity. The abundance of Acidobacteria, Actinobacteria, Nitrospirae and Firmicutes were increased by some of the applied materials, which could promote plant growth, change Cd bioavailability and reduce Cd toxicity. These findings indicated that the applied environment functional materials could facilitate the phytoremediation of Cd contaminated environment by changing Cd fractions, sediments properties and bacterial community structure.

Biochar facilitated the phytoremediation of cadmium contaminated sediments: Metal behavior, plant toxicity, and microbial activity.

Cadmium (Cd) contamination in river sediments becomes increasingly serious, and phytoremediation has been used to remediate Cd contaminated sediments, but the remediation efficiency needs to be improved. In this study, tea waste derived biochar (TB) was used to facilitate the phytoremediation of Cd contaminated sediments. Results showed that TB at 100, 500 and 1000 mg kg-1 increased Cd accumulation and translocation in ramie seedlings by changing Cd speciation in sediments and altering the subcellular distribution of Cd in plant cells. TB at low contents alleviated Cd induced toxicity in ramie seedlings by promoting plant growth and mitigating the oxidative stress. In addition, the activities of urease-, phosphatase-, and catalase-producing microbes in the Cd contaminated sediments were promoted by the application of TB. These findings demonstrated that biochar at low concentrations could improve the phytoremediation efficiency and mitigating Cd-induced toxicity to plants and microbes in Cd contaminated sediments. This study herein provides a novel technological application of waste biomass in controlling and mitigating risks of heavy metals.

Nanoscale zero-valent iron assisted phytoremediation of Pb in sediment: Impacts on metal accumulation and antioxidative system of Lolium perenne.

Lead (Pb) is a highly toxic environmental pollutant, and could result in toxic effects on living organisms. The effects of 0, 100, 200, 500, 1000 and 2000 mg/kg of nZVI on plant growth, Pb accumulation and antioxidative responses of Lolium perenne were investigated. Results showed that the total Pb contents in L. perenne with the treatment of low concentrations of nZVI (100, 200 and 500 mg/kg) were higher than those in the non-nZVI treatments, and the highest Pb accumulation capacity of 1175.40 µg per pot was observed in L. perenne with the treatment of 100 mg/kg nZVI. However, the total Pb contents in L. perenne decreased at high concentrations of nZVI (1000 and 2000 mg/kg). This might be resulted from the decrease of photosynthetic chlorophyll content and the aggravated oxidative stress induced by the high concentration of nZVI, which caused the decrease of plant biomass and metal accumulation capacity in plant. Moreover, the sequential extraction experiments results showed that the lowest acid soluble fraction of Pb in the sediments was found in the treatment with 100 mg/kg of nZVI, indicating that 100 mg/kg was the optimum concentration for nZVI to assist the phytoremediation of Pb-polluted sediment. To conclude, these findings provide a promising method to remediate Pb-polluted sediment by nZVI assisted phytoremediation.

Stabilized Nanoscale Zerovalent Iron Mediated Cadmium Accumulation and Oxidative Damage of Boehmeria nivea (L.) Gaudich Cultivated in Cadmium Contaminated Sediments.

Nanoparticles can be absorbed by plants, but their impacts on phytoremediation are not yet well understood. This study was carried out to determine the impacts of starch stabilized nanoscale zerovalent iron (S-nZVI) on the cadmium (Cd) accumulation and the oxidative stress in Boehmeria nivea (L.) Gaudich (ramie). Plants were cultivated in Cd-contaminated sediments amended with S-nZVI at 100, 500, and 1000 mg/kg, respectively. Results showed that S-nZVI promoted Cd accumulation in ramie seedlings. The subcellular distribution result showed that Cd content in cell wall of plants reduced, and its concentration in cell organelle and soluble fractions increased at S-nZVI treatments, indicating the promotion of Cd entering plant cells by S-nZVI. In addition, the 100 mg/kg S-nZVI alleviated the oxidative damage to ramie under Cd-stress, while 500 and 1000 mg/kg S-nZVI inhibited plant growth and aggravated the oxidative damage to plants. These findings demonstrate that nanoparticles at low concentration can improve the efficiency of phytoremediation. This study herein develops a promising novel technique by the combined use of nanotechnology and phytoremediation in the remediation of heavy metal contaminated sites.

Effects of calcium at toxic concentrations of cadmium in plants.

MAIN CONCLUSION: This review provides new insight that calcium plays important roles in plant growth, heavy metal accumulation and translocation, photosynthesis, oxidative damage and signal transduction under cadmium stress. Increasing heavy metal pollution problems have raised word-wide concerns. Cadmium (Cd), being a highly toxic metal, poses potential risks both to ecosystems and human health. Compared with conventional technologies, phytoremediation, being cost-efficient, highly stable and environment-friendly, is believed to be a promising green technology for Cd decontamination. However, Cd can be easily taken up by plants and may cause severe phytotoxicity to plants, thus limiting the efficiency of phytoremediation. Various researches are being done to investigate the effects of exogenous substances on the mitigation of Cd toxicity to plants. Calcium (Ca) is an essential plant macronutrient that involved in various plant physiological processes, such as plant growth and development, cell division, cytoplasmic streaming, photosynthesis and intracellular signaling transduction. Due to the chemical similarity between Ca and Cd, Ca may mediate Cd-induced physiological or metabolic changes in plants. Recent studies have shown that Ca could be used as an exogenous substance to protect plants against Cd stress by the alleviation of growth inhibition, regulation of metal uptake and translocation, improvement of photosynthesis, mitigation of oxidative damages and the control of signal transduction in the plants. The effects of Ca on toxic concentrations of Cd in plants are reviewed. This review also provides new insight that plants with enhanced Ca level have improved resistance to Cd stress.

Composting of 4-nonylphenol-contaminated river sediment with inocula of Phanerochaete chrysosporium.

A composting study was performed to investigate the degradation of 4-nonylphenol (4-NP) in river sediment by inoculating Phanerochaete chrysosporium (Pc). Pc was inoculated into composting Reactor A, C and D, while Reactor B without inocula was used as control. The results showed that composting with Pc accelerated the degradation of 4-NP, increased the catalase and polyphenol oxidase enzyme activities in contaminated sediment. The dissipation half-life (t1/2) of 4-NP in Reactor A, C and D with inocula of Pc were 2.079, 2.558, 2.424days, while in Reactor B without inocula of Pc it was 3.239days, respectively. Correlation analysis showed that the contents of 4-NP in sediment in Reactor A and D were negatively correlated with the actives of laccase, whereas no obvious correlation was observed in Reactor B and C. All these findings also indicated that Pc enhanced the maturity of compost, and the best composting C/N ratio was 25.46:1.

Effects of exogenous calcium and spermidine on cadmium stress moderation and metal accumulation in Boehmeria nivea (L.) Gaudich.

Cadmium (Cd) is a detrimental metal in the environment and it is easily taken up by plants, thus entering the food chain and posing a severe threat to human health. Phytoremediation being low cost, highly stable, and environmentally friendly has been considered as a promising green technology for Cd remediation. The addition of exogenous substances to the culture media has been recognized as an efficient strategy to improve plant phytoremediation capability. Pot trials were conducted to investigate the combined effects of exogenous calcium (Ca) and spermidine (Spd) on Cd-induced toxicity in Boehmeria nivea (L.) Gaudich. (ramie). Results showed that the application of 5-mM exogenous Ca significantly alleviated Cd toxicity in ramie by reducing Cd accumulation, depressing H2O2 and malondialdehyde contents, increasing plants dry weights and chlorophyll concentrations, as well as altering the activities of total superoxide dismutase and guaiacol peroxidase. Furthermore, as a non-Cd hyperaccumulator plant, ramie hyperaccumulated Cd and suffered more severe toxic effects of Cd by the treatment of 1 mM Ca/Cd. The aggravated Cd toxicity could be compensated by the addition of exogenous Spd via the promotion of plant growth and the reduction of the oxidative stress. Overall, the combination effects of 1 mM Ca and Spd appeared to be more superior compared to other treatments in the plants under Cd stress with a higher Cd accumulation ability and the evaluated Cd stress tolerance.

Effects of selenium and silicon on enhancing antioxidative capacity in ramie (Boehmeria nivea (L.) Gaud.) under cadmium stress.

Hydroponic experiments were performed to investigate the ameliorating effects and mitigation mechanisms of selenium and silicon on Cd toxicity in Boehmeria nivea (L.) Gaud. Metal accumulation, chlorophyll content, activities of antioxidant enzymes, and antioxidant contents in ramie were evaluated. The results revealed that cadmium was mainly accumulated in the roots of plants rather than in the aerial parts. Additionally, under 5 mg L(-1) Cd stress, both Se (1 µmol L(-1)) and Si (1 mmol L(-1)) treatments decreased the Cd concentrations in plants. Besides, the treatments also inhibited the translocation ability of Cd from roots to the aboveground parts, which might be related to the decline of generation of reactive oxygen species (ROS). The application of Se and/or Si ameliorated Cd toxicity via stimulating the activities of antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD), and ascorbate peroxidase (APX), which resulted in the significant decrease of the contents of malondialdialdehyde (MDA) and hydrogen peroxide (H2O2) in ramie leaves. In addition, the content of nonenzymatic antioxidant such as glutathione (GSH) was increased significantly through the addition of selenite and silicate. Also, ascorbate (AsA) and vitamin E played a crucial role in scavenging excess ROS within plants. On the whole, appropriate doses of Se and Si were found to benefit plant growth and enhance the ability of ramie to alleviate Cd-induced stress. Moerover, the effects of combination of Se and Si appeared to be more superior compared to addition separately in response to Cd stress.

Structure of the Na,K-ATPase regulatory protein FXYD2b in micelles: implications for membrane-water interfacial arginines.

FXYD2 is a membrane protein responsible for regulating the function of the Na,K-ATPase in mammalian kidney epithelial cells. Here we report the structure of FXYD2b, one of two splice variants of the protein, determined by NMR spectroscopy in detergent micelles. Solid-state NMR characterization of the protein embedded in phospholipid bilayers indicates that several arginine side chains may be involved in hydrogen bond interactions with the phospholipid polar head groups. The structure and the NMR data suggest that FXYD2b could regulate the Na,K-ATPase by modulating the effective membrane surface electrostatics near the ion binding sites of the pump.

[Preventive effect of ganlong capsule on chronic alcoholic hepatic injury in rats].

OBJECTIVE: To study the preventive effect of Ganlong capsule on chronic alcoholic hepatic injury in rats and its mechanism. METHOD: The rat chronic hepatic injury model was induced by intragastrically administered with gradient alcohol, once a day for 12 weeks. Efforts were made to detect the content of ALT, AST, TG, CHO, TNF-alpha in rat serum and GSH, SOD, MDA, ADH, Alb in hepatic tissues were detected, conduct a hepatic pathological examination, and pathological injury grading for livers. RESULT: Ganlong capsule could reduce the content of ALT, AST, TG in blood serum, MDA in hepatic tissues (P < 0.05), and enhance the activities of antioxidants such as SOD and GSH in hepatic tissues (P < 0.05). According to the liver histopathological observation, most structures of hepatic lobules in the model group were destroyed, with disordered liver cell cords, diffuse fat empty bubbles of different sizes in cytoplasm, focal necrosis and infiltration of inflammatory cells. All of treatment groups showed alleviation in rat liver injury to varying degrees. CONCLUSION: Ganlong capsule has a significant preventive effect to chronic alcoholic hepatic injury in rats.

The structure of genetically modified iron-sulfur cluster F(x) in photosystem I as determined by X-ray absorption spectroscopy.

Photosystem I (PS I) mediates light-induced electron transfer from P700 through a chlorophyll a, a quinone and a [4Fe-4S] iron-sulfur cluster F(X), located on the core subunits PsaA/B to iron-sulfur clusters F(A/B) on subunit PsaC. Structure function relations in the native and in the mutant (psaB-C565S/D566E) of the cysteine ligand of F(X) cluster were studied by X-ray absorption spectroscopy (EXAFS) and transient spectroscopy. The structure of F(X) was determined in PS I lacking clusters F(A/B) by interruption of the psaC2 gene of PS I in the cyanobacterium Synechocystis sp PCC 6803. PsaC-deficient mutant cells assembled the core subunits of PS I which mediated electron transfer mostly to the phylloquinone. EXAFS analysis of the iron resolved a [4Fe-4S] cluster in the native PsaC-deficient PS I. Each iron had 4 sulfur and 3 iron atoms in the first and second shells with average Fe-S and Fe-Fe distances of 2.27 A and 2.69 A, respectively. In the C565S/D566E serine mutant, one of the irons of the cluster was ligated to three oxygen atoms with Fe-O distance of 1.81 A. The possibility that the structural changes induced an increase in the reorganization energy that consequently decreased the rate of electron transfer from the phylloquinone to F(X) is discussed.

Structures of the FXYD regulatory proteins in lipid micelles and membranes.

The FXYD membrane proteins constitute a family of conserved auxiliary subunits of the Na,K-ATPase, and have been the focus of recent attention due to their ability to finely regulate the activity of the enzyme complex in various physiological settings. In this review we describe the structures of the proteins, as well as their dynamics and their associations with the lipid bilayer membrane, which we have recently determined by NMR spectroscopy. Although the proteins are relatively small, their genes contain as many as six to nine small exons, and the coincidence of structured protein segments with their genetic elements suggests assembly from discrete structural modules through exon shuffling. The three-dimensional structures and backbone dynamics provide the foundation for understanding their intra-membrane association with the Na,K-ATPase alpha subunit, and the structure of FXYD1 suggests a mechanism whereby the phosphorylation of conserved Ser residues, by protein kinases A and C, could induce a conformational change in the cytoplasmic domain of the protein, to modulate its interaction with the alpha subunit.

Nuclear magnetic resonance structural studies of membrane proteins in micelles and bilayers.

Nuclear magnetic resonance (NMR) spectroscopy enables determination of membrane protein structures in lipid environments, such as micelles and bilayers. This chapter outlines the steps for membrane-protein structure determination using solution NMR with micelle samples, and solid-state NMR with oriented lipid-bilayer samples. The methods for protein expression and purification, sample preparation, and NMR experiments are described and illustrated with examples from gamma and CHIF, two membrane proteins that function as regulatory subunits of the Na+- and K+-ATPase.

NMR of membrane proteins in micelles and bilayers: the FXYD family proteins.

Determining the atomic resolution structures of membrane proteins is of particular interest in contemporary structural biology. Helical membrane proteins constitute one-third of the expressed proteins encoded in a genome, many drugs have membrane-bound proteins as their receptors, and mutations in membrane proteins result in human diseases. Although integral membrane proteins provide daunting technical challenges for all methods of protein structure determination, nuclear magnetic resonance (NMR) spectroscopy can be an extremely versatile and powerful method for determining their structures and characterizing their dynamics, in lipid environments that closely mimic the cell membranes. Once milligram amounts of isotopically labeled protein are expressed and purified, micelle samples can be prepared for solution NMR analysis, and lipid bilayer samples can be prepared for solid-state NMR analysis. The two approaches are complementary and can provide detailed structural and dynamic information. This paper describes the steps for membrane protein structure determination using solution and solid-state NMR. The methods for protein expression and purification, sample preparation and NMR experiments are described and illustrated with examples from the FXYD proteins, a family of regulatory subunits of the Na,K-ATPase.

Conformation of membrane-associated proapoptotic tBid.

The proapoptotic Bcl-2 family protein Bid is cleaved by caspase-8 to release the C-terminal fragment tBid, which translocates to the outer mitochondrial membrane and induces massive cytochrome c release and cell death. In this study, we have characterized the conformation of tBid in lipid membrane environments, using NMR and CD spectroscopy with lipid micelle and lipid bilayer samples. In micelles, tBid adopts a unique helical conformation, and the solution NMR (1)H/(15)N HSQC spectra have a single well resolved resonance for each of the protein amide sites. In lipid bilayers, tBid associates with the membrane with its helices parallel to the membrane surface and without trans-membrane helix insertion, and the solid-state NMR (1)H/(15)N polarization inversion with spin exchange at the magic angle spectrum has all of the amide resonances centered at (15)N chemical shift (70-90 ppm) and (1)H-(15)N dipolar coupling (0-5 kHz) frequencies associated with NH bonds parallel to the bilayer surface, with no intensity at frequencies associated with NH bonds in trans-membrane helices. Thus, the cytotoxic activity of tBid at mitochondria may be similar to that observed for antibiotic polypeptides, which bind to the surface of bacterial membranes as amphipathic helices and destabilize the bilayer structure, promoting the leakage of cell contents.

Control of electron transport in photosystem I by the iron-sulfur cluster FX in response to intra- and intersubunit interactions.

Photosystem I (PS I) is a transmembranal multisubunit complex that mediates light-induced electron transfer from plactocyanine to ferredoxin. The electron transfer proceeds from an excited chlorophyll a dimer (P700) through a chlorophyll a (A0), a phylloquinone (A1), and a [4Fe-4S] iron-sulfur cluster FX, all located on the core subunits PsaA and PsaB, to iron-sulfur clusters FA and FB, located on subunit PsaC. Earlier, it was attempted to determine the function of FX in the absence of FA/B mainly by chemical dissociation of subunit PsaC. However, not all PsaC subunits could be removed from the PS I preparations by this procedure without partially damaging FX. We therefore removed subunit PsaC by interruption of the psaC2 gene of PS I in the cyanobacterium Synechocystis sp. PCC 6803. Cells could not grow under photosynthetic conditions when subunit PsaC was deleted, yet the PsaC-deficient mutant cells grew under heterotrophic conditions and assembled the core subunits of PS I in which light-induced electron transfer from P700 to A1 occurred. The photoreduction of FX was largely inhibited, as seen from direct measurement of the extent of electron transfer from A1 to FX. From the crystal structure it can be seen that the removal of subunits PsaC, PsaD, and PsaE in the PsaC-deficient mutant resulted in the braking of salt bridges between these subunits and PsaB and PsaA and the formation of a net of two negative surface charges on PsaA/B. The potential induced on FX by these surface charges is proposed to inhibit electron transport from the quinone. In the complete PS I complex, replacement of a cysteine ligand of FX by serine in site-directed mutation C565S/D566E in subunit PsaB caused an approximately 10-fold slow down of electron transfer from the quinone to FX without much affecting the extent of this electron transfer compared with wild type. Based on these and other results, we propose that FX might have a major role in controlling electron transfer through PS I.

Stabilization of iron-sulfur cluster F(X) by intra-subunit interactions unraveled by suppressor and second site-directed mutations in PsaB of Photosystem I.

Intra-subunit interactions in the environment of the iron-sulfur cluster F(X) in Photosystem I (PS I) of Synechocystis sp. PCC 6803 were studied by site-directed and second site suppressor mutations. In subunit PsaB, the cysteine ligand (C565) of F(X) and a conserved aspartate (D566) adjacent to C565 were modified. The resulting mutants D566E, C556S/D566E, C556H/D566E and C565H/D566E did not assemble PS I in the thylakoids of the cyanobacterium. Yet, this is the first report of cells of the second site-suppressor mutant (D566E/L416P) and of second site-directed mutant (C565S/D566E) in PsaB that could grow autotrophically in light and were found to assemble a stable functional PS I containing all three iron-sulfur centers, F(X) and F(A/B). The newly resolved structure of PS I (PDB 1JB0) was used to interpret the functional interactions among the amino acid residues. It is suggested that the stability of F(X) is supported by a salt bridge formed between D566, which is adjacent to the cysteine ligand C565 of the iron-sulfur cluster located on loop hi, and R703 located at the start of loop jk. Hydrogen bond between R703 and D571 at the start of loop hi further stabilizes the arginine. Lengthening of the side by 1.2 A chain in mutation D566E caused destabilization of F(X). The extended side-chain was compensated for by the Fe-O, which is 0.3 A shorter than the Fe-S bond resulting in stabilization of the F(X) in the double mutations C565S/D566E. The suppressor mutation D566E/L416P allowed greater freedom for the salt bridge E566-R703, thus relieving the pressure introduced by the D566E replacement and enabling the formation of F(X). F(X) and R703 are therefore stabilized through short- and long-range interactions of the inter-helical loops between h-i, j-k and f-g, respectively.