A novel, rapid and simple CdTe quantum dots (QDs) based technology platform was established for selective and sensitive determination of vitamin B6 in aqueous solution. It can perform accurate and reproducible quant...A novel, rapid and simple CdTe quantum dots (QDs) based technology platform was established for selective and sensitive determination of vitamin B6 in aqueous solution. It can perform accurate and reproducible quantification of vitamin B6 in pharmaceutical with satisfactory results.展开更多
The purpose of this study was to elucidate the relationship between percentage of body lipid and individual vitamin B6 contents in the anchovy used for production of Japanese soup stock. The contents of individual vit...The purpose of this study was to elucidate the relationship between percentage of body lipid and individual vitamin B6 contents in the anchovy used for production of Japanese soup stock. The contents of individual vitamin B6 compound in foods should be determined to estimate the functionality of foods. Anchovies (Engraulisjaponica) for use as production of iriko, which is a raw material for preparation of Japanese soup stock, were caught using a medium-sized purse seine on May 26th, June 1st, and July 6th 2011 in Tachibana Bay, Nagasaki, Japan. Vitamin B6 contents were analyzed by 4-pyridoxolacone-coversion (all-enzymatic) HPLC. The relationship between body length, lipid content and the individual contents of vitamin B6 compounds in the anchovies was determined. The propriety of anchovies for iriko preparation could not be estimated based on the appearance of length of fishes. The anchovies were rich in vitamin B6, especially pyridoxamine 5'-phosphate, which may prevent diabetic complications. The percentage of body lipid significantly showed a negative correlation with the content of pyridoxamine 5'-phosphate. The contents of the other vitamin B6 compounds did not show the significant correlation with the percentage of body lipid.展开更多
Background: Anemia is one of the most prevalent complications during pregnancy. It is commonly considered a risk factor for poor pregnancy outcomes and can result in complications that threaten the life of both mother...Background: Anemia is one of the most prevalent complications during pregnancy. It is commonly considered a risk factor for poor pregnancy outcomes and can result in complications that threaten the life of both mother and fetus, such as preterm birth, and low birth weight. There is clear evidence to support prompt treatment in all patients with iron deficiency anemia because it is known that treatment improves quality of life and physical condition as well as alleviates fatigue and cognitive deficits. Objective: The aim of the study was to evaluate the value of addition of vitamin B6 to iron in treatment of iron deficiency anemia in pregnant women during the second trimester. Patients and Methods: The study was done by giving anemia pregnant women iron therapy and vitamin B6 which represent group A and iron therapy alone which represents group B. For each pregnant woman, age, parity and gestational history were taken before treatment. All pregnant women took their allocated treatment regularly for three weeks after diagnosis of iron deficiency anemia with complete blood picture and followed up after three weeks. Results: Results of the study revealed that there was no statistically significant difference between the two groups of therapy according to the hemoglobin level before treatment (p-value = 0.734), statistically significant higher mean value in after treatment than before treatment (p-value = 0.048), there was a significant difference in the rate of change of hemoglobin (p-value = 0.011) and body mass index (p-value 0.001). Conclusion: Iron and vitamin B6 seems to increase hemoglobin level more than iron only. Thus, in pregnant women with iron deficiency anemia iron plus vitamin B6 may be considered as a more effective alternative treatment than iron only.展开更多
Pyridoxal kinase (PLK) (EC 2.7.1.35) catalyzes the ATP-dependent phosphorylation of pyridoxal, generating pyridoxal-5'-phosphate (PLP), an important cofactor for many enzymatic reactions. Bombyx mori, similar t...Pyridoxal kinase (PLK) (EC 2.7.1.35) catalyzes the ATP-dependent phosphorylation of pyridoxal, generating pyridoxal-5'-phosphate (PLP), an important cofactor for many enzymatic reactions. Bombyx mori, similar to mammals, relies on a nutritional source of vitamin B6 to synthesize PLP. This article describes how a cDNA encoding PLK was cloned from Bombyx mori using the PCR method (GenBank accession number: DQ452397). The cDNA has an 894 bp open reading frame and encodes a protein of 298 amino acid residues with a molecular mass of 33.1 k.Da. The amino acid sequence shares 48.6% identity with that of human PLK, and it also contains signature conserved motifs of the PLK family. However, the protein is 10 or more amino acids shorter than the PLK from mammals and plants, and several amino acid residues conserved in the PLK from mammals and plants are changed in the protein. The cDNA cloned was expressed successfully in Escherichia coli using the T7 promoter/T7 RNA polymerase expression system, and the crude extracts containing the expressed product were found to have strong PLK enzymatic activity with a value of 30 nmol/min/mg, confirming that the cDNA encodes the functional PLK of Bombyx mori. This is the first identification of a gene encoding PLK in insects.展开更多
Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy...Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.展开更多
OsPLS4 encodes aβ-ketoacyl carrier protein reductase(KAR).The role of OsPLS4 in rice sheath blight(Rhizoctonia solani)remains unclear.Our preliminary studies showed that premature leaf senescence mutants(pls4)were hi...OsPLS4 encodes aβ-ketoacyl carrier protein reductase(KAR).The role of OsPLS4 in rice sheath blight(Rhizoctonia solani)remains unclear.Our preliminary studies showed that premature leaf senescence mutants(pls4)were highly susceptive to sheath blight in the early stage of rice development.To explore the role of this gene in the development of rice sheath blight,the transcriptome profiles of the rice pls4 mutant and wild type were compared by RNA-seq.The results revealed 2,569 differentially expressed genes(DEGs).The down-regulated genes were significantly enriched in the defense response-related biological processes.These down-regulated genes included the chitinase genes and WRKY genes,which were significantly changed in pls4 mutants.Furthermore,467 genes induced significant alternative splicing(AS)events.Among them,intron retention(IR)affected gene expression levels and functions of the vitamin B6(VB6)metabolism pathway related to sheath blight.This result suggests that IR plays an important role in the sheath blight resistance of mutant pls4.Together,these results indicate that pls4 could be involved in the biological process of sheath blight via DEGs and the fine-tuning of IR.The present study provides a molecular basis for further investigation of the resistance of rice to sheath blight.展开更多
Objective:Immunonutrition represents a diet based on the knowledge of basic principles of the immune system and its functions.Despite numerous claims,the direct comparison of the immunostimulating effects of natural m...Objective:Immunonutrition represents a diet based on the knowledge of basic principles of the immune system and its functions.Despite numerous claims,the direct comparison of the immunostimulating effects of natural modulators is limited,making any conclusions difficult.Our study focused on most common vitamins and immunonutrients and directly compared their effects on various branches of the immune system.Methods:In this study we used a mouse model to evaluate various aspects of immune reactions,namely phagocytic activity,IL-2 secretion,NK cell activity,antibody formation and growth of breast cancer in order to find out the possible effects of six different immunonutrients and their combinations.Results:We found that glucan was in all tests the most active immunomodulator.Synergistic effects were observed only in glucan-selenium and glucan-vitamin C combinations.The rest of immunonutrients had only small activity or no activity at all.Conclusion:Based on our results,we concluded that most of vitamins and minerals have only limited,if any,effects on immune activities including cancer.The current study managed to confirm synergistic effects of the beta glucan-vitamin C and beta-glucan-selenium combinations.More studies on possible positive or negative effects of such combination and on mechanisms of action are important.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge ...Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production.In this study,our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase(SerC)to resolve its redundancy and promiscuity.The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.展开更多
Plants can be infected by multiple pathogens concurrently in natural systems. However,pathogen–pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium sp...Plants can be infected by multiple pathogens concurrently in natural systems. However,pathogen–pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium spp. also cause soybean root rot. In a 3-year field investigation, we discovered that P. sojae and Fusarium spp. frequently coexisted in diseased soybean roots. Out of 336 P. sojae–soybean–Fusarium combinations,more than 80% aggravated disease. Different Fusarium species all enhanced P. sojae infection when co-inoculated on soybean. Treatment with Fusarium secreted non-proteinaceous metabolites had an effect equal to the direct pathogen coinoculation. By screening a Fusarium graminearum mutant library, we identified Fusarium promoting factor of Phytophthora sojae infection 1(Fpp1),encoding a zinc alcohol dehydrogenase. Fpp1 is functionally conserved in Fusarium and contributes to metabolite-mediated infection promotion, in which vitamin B6(VB6) produced by Fusarium is key. Transcriptional and functional analyses revealed that Fpp1 regulates two VB6 metabolism genes, and VB6 suppresses expression of soybean disease resistance-related genes. These results reveal that co-infection with Fusarium promotes loss of P. sojae resistance in soybean, information that will inform the sustainable use of diseaseresistant crop varieties and provide new strategies to control soybean root rot.展开更多
The electrochemistry of pyridoxine (vitamin B6, VB6) was studied by cyclic voltammetry at a glassy carbon electrode. The electrochemical response of VB6 could be significantly enhanced by using 4-hydroxy-2,2,6,6-tetra...The electrochemistry of pyridoxine (vitamin B6, VB6) was studied by cyclic voltammetry at a glassy carbon electrode. The electrochemical response of VB6 could be significantly enhanced by using 4-hydroxy-2,2,6,6-tetra- methylpiperidine-N-oxyl (HO-TEMPO) as a mediator via an electrocatalytic EC' mechanism with the oxoammo-nium ion of HO-TEMPO as the active oxidant. The catalytic rate constant was determined to be 5.4×103 (mol L-1)-1s-1 by using chronoamperometry.展开更多
Vitamin B6 (vitB6) serves as an essential cofactor for more than 140 enzymes. Pyridoxal 5'-phosphate (PLP), active cofactor form of vitB6, can be photolytically destroyed by trace amounts of ultraviolet-B (UV-B...Vitamin B6 (vitB6) serves as an essential cofactor for more than 140 enzymes. Pyridoxal 5'-phosphate (PLP), active cofactor form of vitB6, can be photolytically destroyed by trace amounts of ultraviolet-B (UV-B). How sun-exposed organisms cope with PLP photosensitivity and modulate vitB6 homeostasis is currently unknown. We previously reported on two Arabidopsis mutants, rusl and rus2, that are hypersensitive to trace amounts of UV-B light. We performed mutagenesis screens for second-site suppressors of the rus mutant phenotype and identified mutations in the ASPARTATE AMINOTRANSFERASE2 (ASP2) gene. ASP2 encodes for cytosolic aspartate aminotransferase (AAT), a PLP-dependent enzyme that plays a key role in carbon and nitrogen metabolism. Genetic analyses have shown that specific amino acid substitutions in ASP2 override the phenotypes of rusl and rus2 single mutants as well as rusl rus2 double mutant. These substitutions, all shown to reside at specific positions in the PLP-binding pocket, resulted in no PLP binding. Additional asp2 mutants that abolish AAT enzymatic activity, but which alter amino acids outside of the PLP-binding pocket, fail to suppress the rus phenotype. Furthermore, exogenously adding vitB6 in growth media can rescue both rusl and rus2. Our data suggest that AAT plays a role in vitB6 homeostasis in Arabidopsis.展开更多
Interleukin-33(IL-33)is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis.The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immun...Interleukin-33(IL-33)is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis.The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation,but the mechanism is still unclear.Here,we found that healthy individuals had higher phosphate-pyridoxal(PLP,an active form of vitamin B6)concentrations in the serum than asthma patients.Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation.In a mouse model of lung inflammation,we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33.A mechanistic study showed that in vivo,pyridoxal(PL)needed to be converted into PLP,which inhibited the type 2 response by regulating IL-33 stability.In mice heterozygous for pyridoxal kinase(PDXK),the conversion of PL to PLP was limited,and IL-33 levels were increased in the lungs,aggravating type 2 inflammation.Furthermore,we found that the mouse double minute 2 homolog(MDM2)protein,an E3 ubiquitin-protein ligase,could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells.PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway.In addition,inhalation of PLP alleviated asthma-related effects in mouse models.In summary,our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response,which might help develop a potential preventive and therapeutic agent for allergy-related diseases.展开更多
Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal...Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal immunity is unclear.Here,we show that the effector protein AvrRxo1,an ATPdependent protease,enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1(pyridoxal phosphate synthase),thereby reducing vitamin B6(VB6)levels in rice.VB6 is required for the activity of aldehyde oxidase,which catalyzes the last step of abscisic acid(ABA)biosynthesis,and ABA positively regulates rice stomatal immunity against Xoc.Thus,we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata.Moreover,AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality,including low VB6 levels,of Xoc-infected rice grains.展开更多
Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency an...Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease.Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia,Wilson's disease,deficiencies of divalent ions,or malnutrition.Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis,the use of certain medications,and in bone disease.Finally,subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia.The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.展开更多
YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence o...YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the pariplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal struc- tures of YfiB alone and of an active mutant YfiB^L43P complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiB^L43P adopts a stretched conformation allowing activated YfiB to penebate the peptidoglycan (PG) layer and access YfiR. YfiBL43P shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YflB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YflR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiBL43P-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system.展开更多
基金the National Natural Science Foundation of China (No.20275014)for financially supporting this work.
文摘A novel, rapid and simple CdTe quantum dots (QDs) based technology platform was established for selective and sensitive determination of vitamin B6 in aqueous solution. It can perform accurate and reproducible quantification of vitamin B6 in pharmaceutical with satisfactory results.
文摘The purpose of this study was to elucidate the relationship between percentage of body lipid and individual vitamin B6 contents in the anchovy used for production of Japanese soup stock. The contents of individual vitamin B6 compound in foods should be determined to estimate the functionality of foods. Anchovies (Engraulisjaponica) for use as production of iriko, which is a raw material for preparation of Japanese soup stock, were caught using a medium-sized purse seine on May 26th, June 1st, and July 6th 2011 in Tachibana Bay, Nagasaki, Japan. Vitamin B6 contents were analyzed by 4-pyridoxolacone-coversion (all-enzymatic) HPLC. The relationship between body length, lipid content and the individual contents of vitamin B6 compounds in the anchovies was determined. The propriety of anchovies for iriko preparation could not be estimated based on the appearance of length of fishes. The anchovies were rich in vitamin B6, especially pyridoxamine 5'-phosphate, which may prevent diabetic complications. The percentage of body lipid significantly showed a negative correlation with the content of pyridoxamine 5'-phosphate. The contents of the other vitamin B6 compounds did not show the significant correlation with the percentage of body lipid.
文摘Background: Anemia is one of the most prevalent complications during pregnancy. It is commonly considered a risk factor for poor pregnancy outcomes and can result in complications that threaten the life of both mother and fetus, such as preterm birth, and low birth weight. There is clear evidence to support prompt treatment in all patients with iron deficiency anemia because it is known that treatment improves quality of life and physical condition as well as alleviates fatigue and cognitive deficits. Objective: The aim of the study was to evaluate the value of addition of vitamin B6 to iron in treatment of iron deficiency anemia in pregnant women during the second trimester. Patients and Methods: The study was done by giving anemia pregnant women iron therapy and vitamin B6 which represent group A and iron therapy alone which represents group B. For each pregnant woman, age, parity and gestational history were taken before treatment. All pregnant women took their allocated treatment regularly for three weeks after diagnosis of iron deficiency anemia with complete blood picture and followed up after three weeks. Results: Results of the study revealed that there was no statistically significant difference between the two groups of therapy according to the hemoglobin level before treatment (p-value = 0.734), statistically significant higher mean value in after treatment than before treatment (p-value = 0.048), there was a significant difference in the rate of change of hemoglobin (p-value = 0.011) and body mass index (p-value 0.001). Conclusion: Iron and vitamin B6 seems to increase hemoglobin level more than iron only. Thus, in pregnant women with iron deficiency anemia iron plus vitamin B6 may be considered as a more effective alternative treatment than iron only.
基金This work was supported by the Foundation of Talented Person Development of Anhui Province in 2004.
文摘Pyridoxal kinase (PLK) (EC 2.7.1.35) catalyzes the ATP-dependent phosphorylation of pyridoxal, generating pyridoxal-5'-phosphate (PLP), an important cofactor for many enzymatic reactions. Bombyx mori, similar to mammals, relies on a nutritional source of vitamin B6 to synthesize PLP. This article describes how a cDNA encoding PLK was cloned from Bombyx mori using the PCR method (GenBank accession number: DQ452397). The cDNA has an 894 bp open reading frame and encodes a protein of 298 amino acid residues with a molecular mass of 33.1 k.Da. The amino acid sequence shares 48.6% identity with that of human PLK, and it also contains signature conserved motifs of the PLK family. However, the protein is 10 or more amino acids shorter than the PLK from mammals and plants, and several amino acid residues conserved in the PLK from mammals and plants are changed in the protein. The cDNA cloned was expressed successfully in Escherichia coli using the T7 promoter/T7 RNA polymerase expression system, and the crude extracts containing the expressed product were found to have strong PLK enzymatic activity with a value of 30 nmol/min/mg, confirming that the cDNA encodes the functional PLK of Bombyx mori. This is the first identification of a gene encoding PLK in insects.
文摘Adrenocorticotropic hormone is recommended worldwide as an initial therapy for infantile spasms. However, infantile spasms in about 50% of children cannot be fully controlled by adrenocorticotropic hormone monotherapy, seizures recur in 33% of patients who initially respond to adrenocorticotropic hormone monotherapy, and side effects are relatively common during adrenocorticotropic hormone treatment. Topiramate, vitamin B6, and immunoglobulin are effective in some children with infantile spasms. In the present study, we hypothesized that combined therapy with adrenocorticotropic hormone, topiramate, vitamin B6, and immunoglobulin would effectively treat infantile spasms and have mild adverse effects. Thus, 51 children newly diagnosed with West syndrome including infantile spasms were enrolled and underwent polytherapy with the four drugs. Electroencephalographic hypsarrhythmia was significantly improved in a majority of patients, and these patients were seizure-free, had mild side effects, and low recurrence rates. The overall rates of effective treatment and loss of seizures were significantly higher in cryptogenic children compared with symptomatic children. The mean time to loss of seizures in cryptogenic children was significantly shorter than in symptomatic patients. These findings indicate that initial polytherapy with adrenocorticotropic hormone, topiramate, vitamin Be, and immunoglobulin effectively improves the prognosis of infantile spasms, and its effects were superior in cryptogenic children to symptomatic children.
基金supported by a grant from the Double Thousand Plan of Jiangxi Province(No.jxsq2019101057)the National Natural Science Foundation of China(No.3196150349)to Haihui Fu and Xu Jie,respectively.
文摘OsPLS4 encodes aβ-ketoacyl carrier protein reductase(KAR).The role of OsPLS4 in rice sheath blight(Rhizoctonia solani)remains unclear.Our preliminary studies showed that premature leaf senescence mutants(pls4)were highly susceptive to sheath blight in the early stage of rice development.To explore the role of this gene in the development of rice sheath blight,the transcriptome profiles of the rice pls4 mutant and wild type were compared by RNA-seq.The results revealed 2,569 differentially expressed genes(DEGs).The down-regulated genes were significantly enriched in the defense response-related biological processes.These down-regulated genes included the chitinase genes and WRKY genes,which were significantly changed in pls4 mutants.Furthermore,467 genes induced significant alternative splicing(AS)events.Among them,intron retention(IR)affected gene expression levels and functions of the vitamin B6(VB6)metabolism pathway related to sheath blight.This result suggests that IR plays an important role in the sheath blight resistance of mutant pls4.Together,these results indicate that pls4 could be involved in the biological process of sheath blight via DEGs and the fine-tuning of IR.The present study provides a molecular basis for further investigation of the resistance of rice to sheath blight.
文摘Objective:Immunonutrition represents a diet based on the knowledge of basic principles of the immune system and its functions.Despite numerous claims,the direct comparison of the immunostimulating effects of natural modulators is limited,making any conclusions difficult.Our study focused on most common vitamins and immunonutrients and directly compared their effects on various branches of the immune system.Methods:In this study we used a mouse model to evaluate various aspects of immune reactions,namely phagocytic activity,IL-2 secretion,NK cell activity,antibody formation and growth of breast cancer in order to find out the possible effects of six different immunonutrients and their combinations.Results:We found that glucan was in all tests the most active immunomodulator.Synergistic effects were observed only in glucan-selenium and glucan-vitamin C combinations.The rest of immunonutrients had only small activity or no activity at all.Conclusion:Based on our results,we concluded that most of vitamins and minerals have only limited,if any,effects on immune activities including cancer.The current study managed to confirm synergistic effects of the beta glucan-vitamin C and beta-glucan-selenium combinations.More studies on possible positive or negative effects of such combination and on mechanisms of action are important.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
基金This work was supported by the National Key R&D Program of China(2022YFC2106100)National Natural Science Foundation of China(22178372,32200049)+2 种基金National Science Fund for Distinguished Young Scholars(22325807)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-011,TSBICIP-CXRC-055)Yellow River Delta Industry Leading Talents(DYRC20190212).
文摘Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production.In this study,our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase(SerC)to resolve its redundancy and promiscuity.The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.
基金supported by grants from the National Natural Science Foundation of China (3217237431721004)the China Agriculture Research System (CARS-004-PS14)。
文摘Plants can be infected by multiple pathogens concurrently in natural systems. However,pathogen–pathogen interactions have rarely been studied. In addition to the oomycete Phytophthora sojae, fungi such as Fusarium spp. also cause soybean root rot. In a 3-year field investigation, we discovered that P. sojae and Fusarium spp. frequently coexisted in diseased soybean roots. Out of 336 P. sojae–soybean–Fusarium combinations,more than 80% aggravated disease. Different Fusarium species all enhanced P. sojae infection when co-inoculated on soybean. Treatment with Fusarium secreted non-proteinaceous metabolites had an effect equal to the direct pathogen coinoculation. By screening a Fusarium graminearum mutant library, we identified Fusarium promoting factor of Phytophthora sojae infection 1(Fpp1),encoding a zinc alcohol dehydrogenase. Fpp1 is functionally conserved in Fusarium and contributes to metabolite-mediated infection promotion, in which vitamin B6(VB6) produced by Fusarium is key. Transcriptional and functional analyses revealed that Fpp1 regulates two VB6 metabolism genes, and VB6 suppresses expression of soybean disease resistance-related genes. These results reveal that co-infection with Fusarium promotes loss of P. sojae resistance in soybean, information that will inform the sustainable use of diseaseresistant crop varieties and provide new strategies to control soybean root rot.
基金Project supported by the National Natural Science Foundation of China (Nos. 20172025 and 20332020).
文摘The electrochemistry of pyridoxine (vitamin B6, VB6) was studied by cyclic voltammetry at a glassy carbon electrode. The electrochemical response of VB6 could be significantly enhanced by using 4-hydroxy-2,2,6,6-tetra- methylpiperidine-N-oxyl (HO-TEMPO) as a mediator via an electrocatalytic EC' mechanism with the oxoammo-nium ion of HO-TEMPO as the active oxidant. The catalytic rate constant was determined to be 5.4×103 (mol L-1)-1s-1 by using chronoamperometry.
文摘Vitamin B6 (vitB6) serves as an essential cofactor for more than 140 enzymes. Pyridoxal 5'-phosphate (PLP), active cofactor form of vitB6, can be photolytically destroyed by trace amounts of ultraviolet-B (UV-B). How sun-exposed organisms cope with PLP photosensitivity and modulate vitB6 homeostasis is currently unknown. We previously reported on two Arabidopsis mutants, rusl and rus2, that are hypersensitive to trace amounts of UV-B light. We performed mutagenesis screens for second-site suppressors of the rus mutant phenotype and identified mutations in the ASPARTATE AMINOTRANSFERASE2 (ASP2) gene. ASP2 encodes for cytosolic aspartate aminotransferase (AAT), a PLP-dependent enzyme that plays a key role in carbon and nitrogen metabolism. Genetic analyses have shown that specific amino acid substitutions in ASP2 override the phenotypes of rusl and rus2 single mutants as well as rusl rus2 double mutant. These substitutions, all shown to reside at specific positions in the PLP-binding pocket, resulted in no PLP binding. Additional asp2 mutants that abolish AAT enzymatic activity, but which alter amino acids outside of the PLP-binding pocket, fail to suppress the rus phenotype. Furthermore, exogenously adding vitB6 in growth media can rescue both rusl and rus2. Our data suggest that AAT plays a role in vitB6 homeostasis in Arabidopsis.
基金the Ministry of Science and Technology of China(2018YFA0507402)the National Natural Science Foundation of China(32000667,81925001,and 82170051)+2 种基金the Shanghai Science and Technology Innovation Action(21ZR1470600,21JC1405800 and 20S11901800)the Key Scientific Innovation project of the Shanghai Municipal Education Commission(No.202101070007-E00097)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2022264).
文摘Interleukin-33(IL-33)is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis.The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation,but the mechanism is still unclear.Here,we found that healthy individuals had higher phosphate-pyridoxal(PLP,an active form of vitamin B6)concentrations in the serum than asthma patients.Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation.In a mouse model of lung inflammation,we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33.A mechanistic study showed that in vivo,pyridoxal(PL)needed to be converted into PLP,which inhibited the type 2 response by regulating IL-33 stability.In mice heterozygous for pyridoxal kinase(PDXK),the conversion of PL to PLP was limited,and IL-33 levels were increased in the lungs,aggravating type 2 inflammation.Furthermore,we found that the mouse double minute 2 homolog(MDM2)protein,an E3 ubiquitin-protein ligase,could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells.PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway.In addition,inhalation of PLP alleviated asthma-related effects in mouse models.In summary,our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response,which might help develop a potential preventive and therapeutic agent for allergy-related diseases.
基金This study was supported by the National Natural Science Foundation(31872925 and 32072500)Natural Science Outstanding Youth Fund of Shandong Province(JQ201807)+3 种基金Shandong Province Key Research and Development Plan(2019JZZY020608,2020CXGC010803,and 2019GN C106152)Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province(2019KJF023)the National Key Research and Development Program of China(2016YFD0100903)X.D.thanks S.H.for hosting his research visit at Mich-igan State University,supported by the United States National Institute of General Medical Sciences(GM109928).
文摘Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal immunity is unclear.Here,we show that the effector protein AvrRxo1,an ATPdependent protease,enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1(pyridoxal phosphate synthase),thereby reducing vitamin B6(VB6)levels in rice.VB6 is required for the activity of aldehyde oxidase,which catalyzes the last step of abscisic acid(ABA)biosynthesis,and ABA positively regulates rice stomatal immunity against Xoc.Thus,we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata.Moreover,AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality,including low VB6 levels,of Xoc-infected rice grains.
文摘Subnormal levels of liver enzymes,below the lower limit of normal on local laboratory reports,can be useful diagnostically.For instance,subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease.Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia,Wilson's disease,deficiencies of divalent ions,or malnutrition.Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis,the use of certain medications,and in bone disease.Finally,subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia.The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.
文摘YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the pariplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal struc- tures of YfiB alone and of an active mutant YfiB^L43P complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiB^L43P adopts a stretched conformation allowing activated YfiB to penebate the peptidoglycan (PG) layer and access YfiR. YfiBL43P shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YflB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YflR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiBL43P-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system.