Crosstalk between 5-Aminolevulinic Acid and Abscisic Acid Adjusted Leaf Iron Accumulation and Chlorophyll Synthesis to Enhance the Cold Tolerance in Solanum lycopersicum Seedlings.

Previous studies found that 5-aminolevulinic acid (ALA) and abscisic acid (ABA) can mitigate damage from adversity by enhancing photosynthesis. However, it is not clear whether they have positive effects on iron utilization and chlorophyll synthesis of tomato seedlings under low-temperature stress. To investigate the possible functional relationship between ABA and ALA and elucidate the possible mechanisms of action of ALA to alleviate low-temperature stress in tomato seedlings, this experiment analyzed the effects of ALA and ABA on chlorophyll synthesis in tomato seedling leaves sprayed with exogenous of ALA (25 mg·L-1) or ABA (100 µM) under low-temperature stress (8-18 °C/8-12 °C, day/night). The results show that exogenous ALA increased the Fv/Fm of tomato leaves by 5.31% and increased the accumulation of iron and chlorophyll by 101.15% and 15.18%, respectively, compared to the low-temperature treatment alone, and tomato resistance of low-temperature stress was enhanced. Meanwhile, exogenous application of ALA increased the ABA content by 39.43%, and subsequent application of exogenous ABA revealed that tomato seedlings showed similar effects to exogenous ALA under low-temperature stress, with increased accumulation of iron and chlorophyll in tomato seedlings, which eventually increased the maximum photochemical efficiency of PS II. Under low-temperature stress, application of exogenous ABA significantly reduced ALA content, but the expression of key enzyme genes (PPGD, HEMB1, HEME1, and HEMF1), precursors of chlorophyll synthesis by ALA, was significantly elevated, presumably because the increased activity of these enzymes after external application of ABA accelerated ALA consumption. In conclusion, ABA may crosstalk with ALA to improve the photochemical efficiency and low temperature resistance of tomatoes by regulating chlorophyll synthesis and iron accumulation.

PpMYB52 negatively regulates peach bud break through the gibberellin pathway and through interactions with PpMIEL1.

Bud dormancy, which enables damage from cold temperatures to be avoided during winter and early spring, is an important adaptive mechanism of deciduous fruit trees to cope with seasonal environmental changes and temperate climates. Understanding the regulatory mechanism of bud break in fruit trees is highly important for the artificial control of bud break and the prevention of spring frost damage. However, the molecular mechanism underlying the involvement of MYB TFs during the bud break of peach is still unclear. In this study, we isolated and identified the PpMYB52 (Prupe.5G240000.1) gene from peach; this gene is downregulated in the process of bud break, upregulated in response to ABA and downregulated in response to GA. Overexpression of PpMYB52 suppresses the germination of transgenic tomato seeds. In addition, Y2H, Bimolecular fluorescence complementation (BiFC) assays verified that PpMYB52 interacts with a RING-type E3 ubiquitin ligase, PpMIEL1, which is upregulated during bud break may positively regulate peach bud break by ubiquitination-mediated degradation of PpMYB52. Our findings are the first to characterize the molecular mechanisms underlying the involvement of MYB TFs in peach bud break, increasing awareness of dormancy-related molecules to avoid bud damage in perennial deciduous fruit trees.

Prunus persica transcription factor PpNAC56 enhances heat resistance in transgenic tomatoes.

Members of the NAC (NAM, ATAF1,2 and CUC2) transcription factor family are involved in numerous processes of plant growth and development and play an important role in the response to abiotic stresses such as salinity, drought and heat, but little research on this topic has been done in peach. In this study, we analyzed the expression patterns of PpNAC56 under abiotic stress and found that PpNAC56 responded to high-temperature stress. To verify the function of PpNAC56, we overexpressed this gene in tomato plants and found that, compared with WT plants, the transgenic tomato plants could accumulate more osmoregulatory substances after high-temperature treatment and thus were more heat resistance. Then, using Y2H, BIFC, and pull-down assays, we found that PpNAC56 could interact with PpMIEL1. In addition, Y1H and dual-luciferase assays verified that PpNAC56 could activate the expression of PpHSP17.4 and PpSnRK2D. The above experimental results demonstrate that PpNAC56 plays an important role in the plant response to heat stress.

Genome-wide identification and characterization of the Prunus persica ferredoxin gene family and its role in improving heat tolerance.

Ferredoxin is involved in many biological processes, such as carbon fixation, nitrogen assimilation, chlorophyll metabolism, and fatty acid synthesis, and it plays a role in plant resistance to stress. However, the functions of Fds in peach during stress are unclear. In this study, 11 members of the peach Fd gene family were identified and divided into six groups (I- VI). We carried out bioinformatics analysis on these sequences, analyzed the physical and chemical properties of PpFd protein and the cis-elements in its promoter region, and predicted and compared the differences in gene structure and conserved protein motifs among groups. The results showed that the PpFd protein was highly conserved in plant species. In addition, overexpression of PpFd08 significantly increased the tolerance of transgenic tomato to high-temperature stress. The transcriptome analysis and qRT-PCR results of PpFd08 transgenic apple calli showed that PpFd08 might enhance heat resistance by modulating the expression of heat tolerance related genes. The results of this study provide a new understanding for the further study of the function of PpFd protein in peach and a candidate gene for improving the heat resistance of peach.

Prunus persica Terpene Synthase PpTPS1 Interacts with PpABI5 to Enhance Salt Resistance in Transgenic Tomatoes.

Terpene synthase (TPS) is related to the production of aromatic substances, but there are few studies on the impact of abiotic stress on TPS and its molecular mechanism, especially in peaches. This study found that salt resistance and abscisic acid (ABA) sensitivity of transgenic tomatoes were enhanced by overexpression of PpTPS1. Moreover, it was found that PpTPS1 interacted with and antagonized the expression of the bZIP transcription factor ABA INSENSITIVE 5 (PpABI5), which is thought to play an important role in salt suitability. In addition, PpTCP1, PpTCP13, and PpTCP15 were found to activate the expression of PpTPS1 by yeast one-hybrid (Y1H) and dual-luciferase assays, and they could also be induced by ABA. In summary, PpTPS1 may be involved in the ABA signaling regulatory pathway and play an important role in salt acclimation, providing a new reference gene for the improvement of salt resistance in peaches.

The More the Slower: Self-Inhibition in Supramolecular Chirality Induction, Memory, Erasure, and Reversion.

Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the SP and RP conformers P[5]. Intriguingly, more chiral inducers led to more intensive final chiroptical properties but lower chiral induction rates. Thus, the chiral inducer plays the role of both activator and inhibitor. Such self-inhibition essentially arises from kinetics manipulation of three tandem equilibria. Moreover, the chiroptical properties could be memorized by replacing the chiral inducer with an achiral competitive binder, and the chiroptical signal could be erased and reversed by an antipodal chiral inducer, which also showed the self-inhibition property.

Elastin Structure, Synthesis, Regulatory Mechanism and Relationship With Cardiovascular Diseases.

As the primary component of elastic fibers, elastin plays an important role in maintaining the elasticity and tensile ability of cardiovascular, pulmonary and many other tissues and organs. Studies have shown that elastin expression is regulated by a variety of molecules that have positive and negative regulatory effects. However, the specific mechanism is unclear. Moreover, elastin is reportedly involved in the development and progression of many cardiovascular diseases through changes in its expression and structural modifications once deposited in the extracellular matrix. This review article summarizes the role of elastin in myocardial ischemia-reperfusion, atherosclerosis, and atrial fibrillation, with emphasis on the potential molecular regulatory mechanisms.

High Selective Isomerization of Glucose to Fructose Catalyzed by Amidoximed Polyacrylonitrile.

The isomerization of glucose to fructose provides an important way to expand the utilization of biomass. Herein, an amidoximated polyacrylonitrile (PAO) with an amidoxime functional group was prepared and used as an active heterogeneous catalyst for the isomerization of glucose to fructose. The PAO was characterized by SEM, XPS, and FTIR. The yield of fructose reached 48.9% with a selectivity of 98.6% for a 5 h reaction in aqueous solution at an initial pH of 6.5 and 85 °C. The pH caused a great influence on the conversion of glucose and selectivity of fructose while a little effect on the yield of fructose in the range of pH 5-10. The activation energy of isomerization reaction was evaluated as 79.7 kJ·mol-1. The catalysis mechanism was proposed, and the synergistic effect of oxime and amino groups played an important role in the isomerization of glucose. PAO maintained good catalytic activity after four cycles.

A Survey of Pharmacogenomics Testing Among Physicians, Pharmacists, and Researchers From China.

To elucidate current domestic factors influencing pharmacogenomics (PGx) implementation and its future in China, we conducted a questionnaire survey on PGx applications and testing. A questionnaire-based survey was created on the popular online professional survey platform "Wenjuanxing" (www.wjx.cn) and performed via the social media platform WeChat. Among 422 participants, there were physicians (27.7%), pharmacists (31.3%), and researchers (41.0%). We found that less than 50% of physicians were aware of the importance of PGx in drug therapy, while over 50% of pharmacists and researchers recognized the importance. Only 38.5% of physicians, 40.9% of pharmacists, and 55.5% of researchers concurred that PGx analysis could lower the economic burdens for patients. However, most of the responders affirmed that PGx should be effectively implemented in clinical practices. A lack of sector standards, a lack of clinical research, and a lack of guidelines were found to be the major factors for hindering PGx clinical application. Among drugs associated with PGx assays, the most common were warfarin and clopidogrel. Although PGx research has advanced rapidly in recent years in mainland China, the clinical implementation of PGx has a long way to go.

Identification of Atrial Fibrillation-Associated Genes ERBB2 and MYPN Using Genome-Wide Association and Transcriptome Expression Profile Data on Left-Right Atrial Appendages.

More reliable methods are needed to uncover novel biomarkers associated with atrial fibrillation (AF). Our objective is to identify significant network modules and newly AF-associated genes by integrative genetic analysis approaches. The single nucleotide polymorphisms with nominal relevance significance from the AF-associated genome-wide association study (GWAS) data were converted into the GWAS discovery set using ProxyGeneLD, followed by merging with significant network modules constructed by weighted gene coexpression network analysis (WGCNA) from one expression profile data set, composed of left and right atrial appendages (LAA and RAA). In LAA, two distinct network modules were identified (blue: p = 0.0076; yellow: p = 0.023). Five AF-associated biomarkers were identified (ERBB2, HERC4, MYH7, MYPN, and PBXIP1), combined with the GWAS test set. In RAA, three distinct network modules were identified and only one AF-associated gene LOXL1 was determined. Using human LAA tissues by real-time quantitative polymerase chain reaction, the differentially expressive results of ERBB2, MYH7, and MYPN were observed (p < 0.05). This study first demonstrated the feasibility of fusing GWAS with expression profile data by ProxyGeneLD and WGCNA to explore AF-associated genes. In particular, two newly identified genes ERBB2 and MYPN via this approach contribute to further understanding the occurrence and development of AF, thereby offering preliminary data for subsequent studies.

Protein 4.1 family and ion channel proteins interact to regulate the process of heart failure in rats.

Heart failure (HF) is a major cause of death in cardiovascular diseases worldwide, and its molecular mechanisms and effective prevention strategies remain to be further studied. The myocardial cytoskeleton plays a pivotal role in many heart diseases. However, little is known about the function of the membrane cytoskeleton 4.1 protein family and related regulatory mechanisms in the pathogenesis of HF. In this study, we detected the localization and expression of the protein 4.1 family and ion channel proteins in a rat HF model induced by doxorubicin (DOX), and studied the interactions between them. Our results showed that compared with the control group, the HF group displayed an increased expression level of protein 4.1R and decreased levels of protein 4.1 G and 4.1 N. The Nav1.5 protein levels were significantly increased, while the SERCA2a and Cav1.2 protein levels were significantly decreased in the HF group. Furthermore, there is co-localization and interaction between protein 4.1R and Nav1.5, protein 4.1 G and SERCA2a, protein 4.1 N and Cav1.2, respectively. Taken together, the results indicated that the protein 4.1 family might be involved in the occurrence and development of HF through its interaction with ion channel proteins, suggesting that 4.1 proteins may serve as a novel therapeutic target for HF.

BTB-TAZ Domain Protein PpBT3 modulates peach bud endodormancy by interacting with PpDAM5.

The dormancy-associated MADS-box (DAM) gene DAM5 has crucial roles in bud endodormancy; however, the molecular regulatory mechanism of PpDAM5 in peach (Prunus persica) has not been elucidated. In this study, using yeast two-hybrid screening, we isolated a BTB-TAZ Domain Protein PpBT3, which interacts with PpDAM5 protein, in the peach cultivar 'Chun xue'. As expected, we found that abscisic acid (ABA) maintained bud endodormancy and induced expression of the PpDAM5 gene, and that over-expressing PpDAM5 in Arabidopsis thaliana repressed seed germination. In contrast, over-expressing PpBT3 in A. thaliana promoted seed germination, and conferred resistance to ABA-mediated germination inhibition. Additionally, a qRT-PCR (quantitative real-time polymerase chain reaction) experiment suggested that the transcript level of PpBT3 gradually increased towards the endodormancy release period, which is the opposite trend of the expression pattern of PpDAM5. Our results suggest that PpBT3 modulates peach bud endodormancy by interacting with PpDAM5, thus revealing a new mechanism for regulating bud dormancy of perennial deciduous trees.

PpNUDX8, a Peach NUDIX Hydrolase, Plays a Negative Regulator in Response to Drought Stress.

Drought stress is a serious abiotic stress source that affects the growth and fruit quality of peach trees. However, the molecular mechanism of the NUDIX hydrolase family in peaches in response to drought stress is still unclear. Here, we isolated and identified the PpNUDX8 (Prupe.5G062300.1) gene from the peach NUDIX hydrolase family, and found that PpNUDX8 has a typical NUDIX hydrolase domain. In this study, we performed 15% PEG6000 drought treatment on peach seedlings, and qRT-PCR analysis showed that 15% PEG6000 induced the transcription level of PpNUDX8. Overexpression of PpNUDX8 reduced the tolerance of calli to 4% PEG6000 treatment. Compared with wild-type apple calli, PpNUDX8 transgenic apple calli had a lower fresh weight and higher MDA content. After 15% PEG6000 drought treatment, PpNUDX8 transgenic tobacco had a greater degree of wilting and shorter primary roots than Under control conditions. The chlorophyll, soluble protein, and proline contents in the transgenic tobacco decreased, and the MDA content and relative conductivity increased. At the same time, PpNUDX8 negatively regulated ABA signal transduction and reduced the transcriptional expression of stress response genes. In addition, PpNUDX8 was not sensitive to ABA, overexpression of PpNUDX8 reduced the expression of the ABA synthesis-related gene NCED6 and increases the expression of the ABA decomposition-related gene CYP1 in tobacco, which in turn leads to a decrease in the ABA content in tobacco. In addition, Under control conditions, overexpression of PpNUDX8 destroyed the homeostasis of NAD and reduced nicotinamide adenine dinucleotide (NADH) in tobacco. After 15% PEG6000 drought treatment, the changes in NAD and NADH in PpNUDX8 transgenic tobacco were more severe than those in WT tobacco. In addition, PpNUDX8 also interacted with PpSnRk1γ (Prupe.6G323700.1).

DNA methylation determines the regulation of pregnane X receptor on CYP3A4 expression.

The expression and activity of CYP3A4 vary among individuals. With the development of epigenetics, it is now possible to elucidate interindividual differences in drug-metabolizing enzymes. Here, we aimed to explore the potential relationship between DNA methylation and CYP3A4 expression. We analyzed the effect of a DNA methylation inhibitor, 5-aza-2-deoxycytidine, on pregnane X receptor (PXR) and CYP3A4 expression in HepG2 cells. In addition, pCpGL-CYP3A4-promoter and pCpGL-CYP3A4-enhancer plus promoter plasmids were constructed, methylated, and transfected. We found that treatment with 5-aza-2-deoxycytidine significantly increased the expression of PXR and CYP3A4 in a concentration- and time-dependent manner. In addition, CYP3A4 expression was significantly enhanced by overexpressing PXR via transfection of pSG5-PXR plasmids. Methylation of CYP3A4 enhancer inhibited CYP3A4 transcriptional activity mediated through PXR and inhibited the binding of PXR and CYP3A4 promoter. We also observed that when the promoter and enhancer of CYP3A4 were methylated, CYP3A4 expression did not increase after treatment with rifampicin. In conclusion, the investigation demonstrates that DNA methylation of CYP3A4 enhancer significantly inhibits CYP3A4 expression, mediated through PXR, which is not influenced by rifampicin.

MicroRNA­494 suppresses hypoxia/reoxygenation­induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1.

Acute myocardial infarction can be caused by ischemia/reperfusion (I/R) injury; however, the mechanism underlying I/R is not completely understood. The present study investigated the functions and mechanisms underlying microRNA (miR)­494 in I/R­induced cardiomyocyte apoptosis and autophagy. Hypoxia/reoxygenation (H/R)­treated H9c2 rat myocardial cells were used as an in vitro I/R injury model. Apoptosis and autophagy were analyzed by Cell Counting Kit­8 assay, Lactic dehydrogenase and superoxide dismutase assay, flow cytometry, TUNEL staining and western blotting. Reverse transcription­quantitative PCR demonstrated that, H9c2 cells treated with 12 h hypoxia and 3 h reoxygenation displayed significantly downregulated miR­494 expression levels compared with control cells. Compared with the corresponding negative control (NC) groups, miR­494 mimic reduced H/R­induced cell apoptosis and autophagy, whereas miR­494 inhibitor displayed the opposite effects. Silent information regulator 1 (SIRT1) was identified as a target gene of miR­494. Furthermore, miR­494 inhibitor­mediated effects on H/R­induced cardiomyocyte apoptosis and autophagy were partially reversed by SIRT1 knockdown. Moreover, compared with si­NC, SIRT1 knockdown significantly increased the phosphorylation levels of PI3K, AKT and mTOR in H/R­treated and miR­494 inhibitor­transfected H9c2 cells. Collectively, the results indicated that miR­494 served a protective role against H/R­induced cardiomyocyte apoptosis and autophagy by directly targeting SIRT1, suggesting that miR­494 may serve as a novel therapeutic target for myocardial I/R injury.

Epidemiological and clinical features of pediatric COVID-19.

BACKGROUND: COVID-19 is an extremely severe infectious disease. However, few studies have focused on the epidemiological and clinical characteristics of pediatric COVID-19. This study conducted a retrospective review of the epidemiological and clinical features of COVID-19 in children. METHODS: A retrospective study was conducted on children with a definite diagnosis of COVID-19 in mainland China using the web crawler technique to collect anonymous COVID-19 updates published by local health authorities. RESULTS: Three hundred forty-one children aged 4 days to 14 years with a median age of 7 years were included. Sixty-six percent of pediatric patients were infected via family members with COVID-19. The median incubation period was 9 days (interquartile range, 6 to 13). Asymptomatic cases accounted for 5.9%, of which 30% had abnormal chest radiologic findings. A majority of pediatric COVID-19 cases showed mild to moderate clinical features, and only a few developed severe or critical diseases (0.6% and 0.3%, respectively). Fever (77.9%) and cough (32.4%) were the predominant presenting symptoms of pediatric COVID-19. The pediatric patients had fewer underlying diseases and complications than adults. The treatment modalities for pediatric COVID-19 patients were not as complex as those of adult COVID-19 patients. The overall prognosis of pediatric COVID-19 was benign with a decent recovery. The median time from onset to cure was 16 days (interquartile range, 13 to 21). CONCLUSIONS: Compared to adults, COVID-19 in children has distinct features of epidemiology and clinical manifestations. The findings from this study might help to guide the development of measures to prevent and treat this ongoing global pandemic. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( chictr.org.cn ) identifier: ChiCTR2000030464.

A Highly Efficient Heterogeneous Catalyst of Bimetal-Organic Frameworks for the Epoxidation of Olefin with H2O2.

A series of bimetel organic framework MnxCu1-x-MOF were prepared. The MOFs was characterized and analyzed by powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The catalytic activity of the developed catalyst was tested on various olefins by H2O2 as oxidant. The MOFs catalyst exhibits excellent catalytic activity for the epoxidations of various aromatic and cyclic olefins. Particularly, Mn0.1Cu0.9-MOF can achieve 90.2% conversion of styrene with 94.3% selectivity of styrene oxide at 0 °C after reaction 6 h. The MOF exhibited the catalytic activity of inverse temperature effect on epoxidation of styrene. The introduction of copper component can stabilize H2O2 and inhibit its decomposition to a certain extent. The catalyst can be reused at least five cycles without significant loss in activity towards epoxidation.

Incorporation of Gene-Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients.

The narrow therapeutic window of tacrolimus necessitates daily monitoring and predictive algorithms based on genetic and nongenetic factors. In this study, we constructed predictive algorithms for tacrolimus stable dose in a retrospective cohort of 1045 Chinese renal transplant recipients. All patients were genotyped for CYP3A4 20230T>C (rs2242480), CYP3A4 T>C (rs4646437), CYP3A5*3 6898A>G (rs776746), ABCB1 129T>C (rs3213619); ABCB1 c.1236C>T (rs01128503), ABCB1 c.2677G>T/A (rs2032582) and ABCB1 c.3435C>T (rs1045642) polymorphisms, and the effects of gene-gene and gene-environment interactions on the predictive accuracy of algorithm were evaluated. In wild-type CYP3A4 rs2242480 (TT) carriers, patients who took calcium channel blockers had lower tacrolimus stable doses than those without the concomitant medications (P < 1 × 10-4 ). In contrast, there was no significant difference in mutant type patients. Similarly, the tacrolimus stable doses in wild-type CYP3A5 rs776746 carriers who had hypertension were higher than those without hypertension (P = 4.10 × 10-3 ). More importantly, dose-predictive algorithms with interaction terms showed higher accuracy and better performance than those without interaction terms. Our finding suggested that wild-type CYP3A4 rs2242480 (TT) carriers should be more cautious to take tacrolimus when they are coadministrated with calcium channel blockers, and CYP3A5 rs776746 (AA) carriers may need higher tacrolimus dosage when they are in combination with hypertension.

[Rs17042171 at chromosome 4q25 is associated with atrial fibrillation in the Chinese Han population from the central plains].

OBJECTIVE: To determine the correlations of single nucleotide polymorphisms (SNPs) with atrial fibrillation (AF) in the Chinese Han population from the central plains.
 Methods: A total of 168 hospitalized patients, including 56 AF and 112 controls, were recruited in this case-control study. The clinical data were obtained from the medical records. All 5 SNPs, rs337711 in KCNN2, rs11264280 near KCNN3, rs17042171 near PITX2, rs6771157 and rs6795970 in SCN10A, were genotyped using amplification refractory mutation system-polymerase chain reaction or direct sequencing. The χ2 test was used to compare categorical variables and preliminarily examine correlations between the genotype frequencies and AF. Subsequently, a logistic regression model was constructed to determine the associations between the SNPs and AF based on the above screened results. Odds ratios (ORs) and 95% confidence interval (CI) were calculated to assess the strength of the correlations. Moreover, we downloaded the genotype data from the HapMap Project for linkage disequilibrium analysis of rs17042171.
 Results: AF patients were likely to be of older age and longer left atrial diameter and had more coronary artery disease and higher hypertension compared with the control group (P<0.05). Among the 5 SNPs, the frequency distribution of genotype AA for rs17042171 was significantly different between the AF and control groups (P<0.05). After adjusting for several covariates, there was still a high risk ratio in patients with the AA genotype compared with the AC+CC genotype (OR: 5.591, 95%CI 2.176 to 14.365, P-B<0.008). Similarly, stratification analysis on the AA genotype demonstrated significant differences between rs17042171 and persistent AF. However, there were not significant correlations between AF and the control groups for the other 4 SNPs (P<0.05).
 Conclusion: Rs17042171, near PITX2 on chromosome 4q25, is associated with AF susceptibility in the Chinese Han population from the central plains, suggesting that this SNP can provide a new strategy for clinical diagnosis in AF patients.

Pharmacogenomics signature: A novel strategy on the individual differences in drug response.

Patients exhibit a wide heterogeneity in their responses to a drug treatment due to variations in the molecular determinants underlying this heterogeneity. Pharmacogenomics approaches can be used to integrate information on drug responsiveness with alterations in molecular entities, often on a genome-wide scale. However, most of the studies involving pharmacogenomics of specific therapeutics are in their early stages and thus are not ready for clinical utilization. Genotyping studies tackle around a candidate gene approach using genes known to be important in the pharmacokinetics and pharmacodynamics of the administered drugs. However, this approach could miss potentially important genes that influence drug sensitivity through unknown mechanisms. The way to get around this limiting approach is sought after. Here, we introduce and propose a novel concept of pharmacogenomics signature (PGx-S) for elucidating holistically the effects of genetic polymorphisms upon individual variations in drug responses in an attempt to boost the pharmacovigilant capacities of drug responses.