Analysis of Genetic Variation Indicates DNA Shape Involvement in Purifying Selection.

Mol Biol Evol. 2018 May 29;:

Authors: Wang X, Zhou T, Wunderlich Z, Maurano MT, DePace AH, Nuzhdin SV, Rohs R

Abstract
Noncoding DNA sequences, which play various roles in gene expression and regulation, are under evolutionary pressure. Gene regulation requires specific protein-DNA binding events, and our previous studies showed that both DNA sequence and shape readout are employed by transcription factors (TFs) to achieve DNA binding specificity. By investigating the shape-disrupting properties of single nucleotide polymorphisms (SNPs) in human regulatory regions, we established a link between disruptive local DNA shape changes and loss of specific TF binding. Furthermore, we described cases where disease-associated SNPs may alter TF binding through DNA shape changes. This link led us to hypothesize that local DNA shape within and around TF binding sites is under selection pressure. To verify this hypothesis, we analyzed SNP data derived from 216 natural strains of Drosophila melanogaster. Comparing SNPs located in functional and nonfunctional regions within experimentally validated cis-regulatory modules (CRMs) from D. melanogaster that are active in the blastoderm stage of development, we found that SNPs within functional regions tended to cause smaller DNA shape variations. Furthermore, SNPs with higher minor allele frequency were more likely to result in smaller DNA shape variations. The same analysis based on a large number of SNPs in putative CRMs of the D. melanogaster genome derived from DNase I accessibility data confirmed these observations. Taken together, our results indicate that common SNPs in functional regions tend to maintain DNA shape, whereas shape-disrupting SNPs are more likely to be eliminated through purifying selection.

PMID: 29850830 [PubMed - as supplied by publisher]

Computational Drug Repurposing: Current Trends.

Curr Med Chem. 2018 May 29;:

Authors: Karaman B, Sippl W

Abstract
Biomedical discovery has been reshaped upon the exploding digitization of data which can be retrieved from a number of sources, ranging from clinical pharmacology to cheminformatics-driven databases. Now, supercomputing platforms and publicly available resources such as biological, physicochemical, and clinical data, can all be integrated to construct a detailed map of signaling pathways and drug mechanisms of action in relation to drug candidates. Recent advancements in computer-aided data mining have facilitated analyses of 'big data' approaches and the discovery of new indications for pre-existing drugs has been accelerated. Linking gene-phenotype associations to predict novel drug-disease signatures or incorporating molecular structure information of drugs and protein targets with other kinds of data derived from systems biology provide great potential to accelerate drug discovery and improve the success of drug repurposing attempts. In this review, we highlight commonly used computational drug repurposing strategies, including bioinformatic and cheminformatic tools, to integrate large-scale data emerging from the systems biology, and consider both the challenges and opportunities of using this approach. Moreover, we provide successful examples and cases studies that combined various in silico drug-repurposing strategies to predict potential novel uses for known therapeutics.

PMID: 29848268 [PubMed - as supplied by publisher]

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The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

Autoimmun Rev. 2018 May;17(5):440-448

Authors: Segal Y, Dahan S, Sharif K, Bragazzi NL, Watad A, Amital H

Abstract
Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.

PMID: 29526630 [PubMed - indexed for MEDLINE]

Young Man Battles For His Life Against Rare Autoimmune Disease.

Manag Care. 2017 10;26(10):19-20

Authors: Calandra R

Abstract
The author's nephew suffers from a rare form of familial hemophagocytic lymphohistiocytosis. His organs shut down and he's placed in a medically induced coma. Meanwhile, costs mount to $4.9 million, most of it paid by an employer-sponsored health plan.

PMID: 29068294 [PubMed - indexed for MEDLINE]

Pharmacogenomics: From classroom to practice.

Mol Genet Genomic Med. 2018 May 31;:

Authors: Nutter SC, Gálvez-Peralta M

Abstract
Perceptions and challenges connecting Pharmacogenomics taught in classrooms and translationing it to advance pharmacy practice rotations and healthcare settings and potential areas of development.

PMID: 29852540 [PubMed - as supplied by publisher]

A Single Codon Optimization Enhances Recombinant Human TNF-α Vaccine Expression in Escherichia coli.

Biomed Res Int. 2018;2018:3025169

Authors: Chu C, Zhang W, Li J, Wan Y, Wang Z, Duan R, Yu P, Zhao N, Zhang K, Wang S, Hao Q, Li W, Zhang C, Zhang W, Zhang Y, Li M, Xue X

Abstract
As a proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α) plays a pivotal role in various autoimmune diseases such as rheumatoid arthritis (RA). Thus, TNF-α has been defined as a therapeutic target for RA. Although some TNF-α antagonists including neutralizing monoclonal antibodies and soluble receptors have been approved to be successful in attenuating symptoms in patients suffering from RA, the long-term use of these passive immunization reagents could cause some problems like a variable degree of immunogenicity. In the present study, in order to wake up active immune responses of RA patients, we developed a recombinant TNF-α therapeutic vaccine (named mrTNF-PADRE) by coupling a 12-amino acid universal Pan HLA-DR Epitope (PADRE) to the protein. Codon optimization was performed to improve the secondary structure of mrTNF-PADRE mRNA to ensure its heterologous expression. As a result, a single codon synonymous mutation greatly elevated recombinant protein expression (about 30% of the total bacteria proteins) in E. coli as compared with the undetectable expression of the unoptimized gene. Although expressed as insoluble inclusion bodies (IBs), the vaccine can be effectively prepared with a purity of over 95% by IBs washing and one-step gel-infiltration chromatography. By this strategy, a stable yield of 5.2 mg purified mrTNF-PADRE per gram of cell paste could be obtained.

PMID: 29850502 [PubMed - in process]

Clinical Relevant Polymorphisms Affecting Clopidogrel Pharmacokinetics and Pharmacodynamics: Insights from the Puerto Rico Newborn Screening Program.

Int J Environ Res Public Health. 2018 May 30;15(6):

Authors: Hernandez-Suarez DF, Tomassini-Fernandini JC, Cuevas A, Rosario-Berrios AN, Nuñez-Medina HJ, Padilla-Arroyo D, Rivera N, Liriano J, Vega-Roman RK, Renta JY, Melin K, Duconge J

Abstract
Background: Variations in several clopidogrel-pharmacogenes have been linked to clopidogrel response variability and clinical outcomes. We aimed to determine the frequency distribution of major polymorphisms on CYP2C19, PON1, ABCB1 and P2RY12 pharmacogenes in Puerto Ricans. Methods: This was a cross-sectional, population-based study of 200 unrelated "Guthrie" cards specimens from newborns registered in the Puerto Rican newborn screening program (PRNSP) between 2004 and 2014. Taqman® SNP assay techniques were used for genotyping. Results: Minor allele frequencies (MAF) were 46% for PON1 (rs662), 41% for ABCB1 (rs1045642), 14% for CYP2C19*17, 13% for CYP2C19*2, 12% for P2RY12-H2 and 0.3% for CYP2C19*4. No carriers of the CYP2C19*3 variants were detected. All alleles and genotype proportions were found to be in Hardy⁻Weinberg equilibrium (HWE). Overall, there were no significant differences between MAFs of these variants in Puerto Ricans and the general population (n = 453) of the 1000 Genome project, except when comparisons to each individual parental group were performed (i.e., Africans, Europeans and East-Asians; p < 0.05). As expected, the prevalence of these markers in Puerto Ricans most resembled those in the 181 subjects from reference populations of the Americas. Conclusions: These prevalence data provide a necessary groundwork for future clinical studies of clopidogrel pharmacogenetics in Caribbean Hispanics.

PMID: 29848980 [PubMed - in process]

Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.

Fluids Barriers CNS. 2018 May 31;15(1):18

Authors: Stopa EG, Tanis KQ, Miller MC, Nikonova EV, Podtelezhnikov AA, Finney EM, Stone DJ, Camargo LM, Parker L, Verma A, Baird A, Donahue JE, Torabi T, Eliceiri BP, Silverberg GD, Johanson CE

Abstract
BACKGROUND: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.
METHODS: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP. RNA from post-mortem samples of the entire lateral ventricular choroid plexus was extracted from 6 healthy controls (Ctrl), 7 patients with advanced (Braak and Braak stage III-VI) Alzheimer's disease (AD), 4 with frontotemporal dementia (FTD) and 3 with Huntington's disease (HuD). Statistics and agglomerative clustering were accomplished with MathWorks, MatLab; and gene set annotations by comparing input sets to GeneGo ( http://www.genego.com ) and Ingenuity ( http://www.ingenuity.com ) pathway sets. Bonferroni-corrected hypergeometric p-values of < 0.1 were considered a significant overlap between sets.
RESULTS: Pronounced differences in gene expression occurred in CP of advanced AD patients vs. Ctrls. Metabolic and immune-related pathways including acute phase response, cytokine, cell adhesion, interferons, and JAK-STAT as well as mTOR were significantly enriched among the genes upregulated. Methionine degradation, claudin-5 and protein translation genes were downregulated. Many gene expression changes in AD patients were observed in FTD and HuD (e.g., claudin-5, tight junction downregulation), but there were significant differences between the disease groups. In AD and HuD (but not FTD), several neuroimmune-modulating interferons were significantly enriched (e.g., in AD: IFI-TM1, IFN-AR1, IFN-AR2, and IFN-GR2). AD-associated expression changes, but not those in HuD and FTD, were enriched for upregulation of VEGF signaling and immune response proteins, e.g., interleukins. HuD and FTD patients distinctively displayed upregulated cadherin-mediated adhesion.
CONCLUSIONS: Our transcript data for human CP tissue provides genomic and mechanistic insight for differential expression in AD vs. FTD vs. HuD for stromal as well as epithelial components. These choroidal transcriptome characterizations elucidate immune activation, tissue functional resiliency, and CSF metabolic homeostasis. The BCSFB undergoes harmful, but also important functional and adaptive changes in neurodegenerative diseases; accordingly, the enriched JAK-STAT and mTOR pathways, respectively, likely help the CP in adaptive transcription and epithelial repair and/or replacement when harmed by neurodegeneration pathophysiology. We anticipate that these precise CP translational data will facilitate pharmacologic/transgenic therapies to alleviate dementia.

PMID: 29848382 [PubMed - in process]

The Genomic Consultation Service: A clinical service designed to improve patient selection for genome-wide sequencing in British Columbia.

Mol Genet Genomic Med. 2018 May 30;:

Authors: Elliott AM, du Souich C, Adam S, Dragojlovic N, van Karnebeek C, Nelson TN, Lehman A, CAUSES Study, Lynd LD, Friedman JM

Abstract
BACKGROUND: Access to clinical diagnostic genome-wide sequencing (GWS; exome or whole genome sequencing) is limited in British Columbia. The establishment of a translational research initiative (CAUSES) to provide diagnostic genome-wide sequencing for 500 children necessitated the development of a genomic consultation service, a clinical service established to provide consultation for physicians considering GWS for their pediatric patients throughout British Columbia. The Genomic Consultation Service provides patient-specific genomic advice that may include: GWS, multi-gene panel, single gene test, referral to medical genetics for clinical evaluation, or no genetic testing. Here, we describe and evaluate this service.
METHODS: We analyzed referral patterns, patient demographics, clinical indications, and genomic advice provided during the first year of this service. Comparison of outcomes from the first 6 months versus the last 6 months was performed.
RESULTS: A total of 407 referrals (238 males and 169 females [p = .0006]) were processed in the first year. Only children were eligible for referral and average patient age was 8 years. Medical genetics was the most frequent referring discipline, followed by biochemical disease and pediatric neurology, respectively. Most patients (68%) had syndromic intellectual disability. There was a significant difference in the frequency of referrals not appropriate for GWS in the first versus the second 6 months of the service (75/220 vs. 42/187; p = .01) suggesting increasing awareness of testing criteria by referring physicians.
CONCLUSION: This triage service is utilized throughout the province and appears to be an important factor in the high diagnostic rate (>40%) achieved in our GWS program.

PMID: 29851296 [PubMed - as supplied by publisher]

Interrupted CAG expansions in ATXN2 gene expand the genetic spectrum of frontotemporal dementias.

Acta Neuropathol Commun. 2018 May 30;6(1):41

Authors: Fournier C, Anquetil V, Camuzat A, Stirati-Buron S, Sazdovitch V, Molina-Porcel L, Turbant S, Rinaldi D, Sánchez-Valle R, Barbier M, Latouche M, Neuro-CEB Neuropathology Network, Stevanin G, Seilhean D, Brice A, Duyckaerts C, Le Ber I

PMID: 29848387 [PubMed - in process]

Amyloid-β accumulation in the CNS in human growth hormone recipients in the UK.

Acta Neuropathol. 2017 Aug;134(2):221-240

Authors: Ritchie DL, Adlard P, Peden AH, Lowrie S, Le Grice M, Burns K, Jackson RJ, Yull H, Keogh MJ, Wei W, Chinnery PF, Head MW, Ironside JW

Abstract
Human-to-human transmission of Creutzfeldt-Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer's disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy (CAA), regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA.

PMID: 28349199 [PubMed - indexed for MEDLINE]

AIDS Clinical Research in Spain-Large HIV Population, Geniality of Doctors, and Missing Opportunities.

Viruses. 2018 May 30;10(6):

Authors: Soriano V, Ramos JM, Barreiro P, Fernandez-Montero JV

Abstract
The first cases of AIDS in Spain were reported in 1982. Since then over 85,000 persons with AIDS have been cumulated, with 60,000 deaths. Current estimates for people living with HIV are of 145,000, of whom 20% are unaware of it. This explains the still high rate of late HIV presenters. Although the HIV epidemic in Spain was originally driven mostly by injection drug users, since the year 2000 men having sex with men (MSM) account for most new incident HIV cases. Currently, MSM represent over 80% of new yearly HIV diagnoses. In the 80s, a subset of young doctors and nurses working at Internal Medicine hospital wards became deeply engaged in attending HIV-infected persons. Before the introduction of antiretrovirals in the earlier 1990s, diagnosis and treatment of opportunistic infections was their major task. A new wave of infectious diseases specialists was born. Following the wide introduction of triple combination therapy in the late 1990s, drug side effects and antiretroviral resistance led to built a core of highly devoted HIV specialists across the country. Since then, HIV medicine has improved and currently is largely conducted by multidisciplinary teams of health care providers working at hospital-based outclinics, where HIV-positive persons are generally seen every six months. Antiretroviral therapy is currently prescribed to roughly 75,000 persons, almost all attended at clinics belonging to the government health public system. Overall, the impact of HIV/AIDS publications by Spanish teams is the third most important in Europe. HIV research in Spain has classically been funded mostly by national and European public agencies along with pharma companies. Chronologically, some of the major contributions of Spanish HIV research are being in the field of tuberculosis, toxoplasmosis, leishmaniasis, HIV variants including HIV-2, drug resistance, pharmacology, antiretroviral drug-related toxicities, coinfection with viral hepatitis, design and participation in clinical trials with antiretrovirals, immunopathogenesis, ageing, and vaccine development.

PMID: 29848987 [PubMed - in process]

[A retrospective historical study evaluating the safe use of current antidepressants in cardiology practice].

Ter Arkh. 2017;89(12):34-42

Authors: Ivanov SV, Volel BA, Syrkina EA, Ternovaya ES, Troshina DV, Grubova MV, Tolkacheva IA, Rozhkov AN, Simonov AN

Abstract
AIM: To confirm the data available in the literature on the cardiac safety of antidepressants.
SUBJECTS AND METHODS: The archival data of 146 case histories were retrospectively analyzed. A study sample consisted of 96 cardiac inpatients regularly taking an antidepressant for more than 3 days during treatment for the underlying cardiovascular disease. The safe use of antidepressants was evaluated in terms of initial electrocardiogram (ECG) QTc interval changes, systolic and diastolic blood pressures (BP) (SBP and DBP), heart rate (HR), and hemorrhagic complications. The data obtained over periods of 3- and 6-8 days were analyzed.
RESULTS: The sample showed no clinically significant ECG QTc interval changes when taking regularly antidepressants within 8 days. Analysis of the dynamics of BP and HR in patients receiving antidepressants revealed no statistically significant differences in these indicators before and 3 and 6-8 days after drug administration. No case of hemorrhagic complications was seen in the study group taking antidepressants.
CONCLUSION: The investigation generally confirms the high cardiac safety of new-generation antidepressants within at least the first week of therapy. Noteworthy are the low daily drug dosages (relatively specified in the instructions) that are sufficient for most cardiac patients with depressive disorders and an additional factor for minimizing adverse reactions.

PMID: 29411758 [PubMed - indexed for MEDLINE]

Immune-related musculoskeletal toxicities among cancer patients treated with immune checkpoint inhibitors: a systematic review.

Immunotherapy. 2017 Nov;9(14):1175-1183

Authors: Abdel-Rahman O, Eltobgy M, Oweira H, Giryes A, Tekbas A, Decker M

Abstract
AIM: Immune-related musculoskeletal toxicities are uncommon but potentially serious adverse events; and they may accompany the use of immune checkpoint inhibitors (ICIs). The objective of this systematic review is to assess the patterns of these musculoskeletal toxicities.
METHODS & RESULTS: PubMed database has been searched till May 2017. Clinical studies and case reports reporting the occurrence of immune-related musculoskeletal toxicities (other than arthralgia and myalgia) in cancer patients treated with ICIs were included. Eight trials with 2263 participants were included. Likewise, nine case reports reporting the outcomes of 12 patients were included.
CONCLUSION: Immune-related arthritis and myositis occur uncommonly in cancer patients treated with ICIs. Further studies are required to better describe the pathogenesis as well as the time course of these events.

PMID: 29067884 [PubMed - indexed for MEDLINE]

Completeness of reporting of adverse events in trials of maintenance immunosuppression in kidney transplantation: a systematic review.

Nephrol Dial Transplant. 2017 Sep 01;32(9):1586-1594

Authors: Howell M, Yeo R, Tong A, Craig JC, Howard K, Wong G

Abstract
Background: Decision-making regarding immunosuppression after transplantation relies on robust evidence on the benefits and harms of available drugs. We aimed to evaluate the reporting of adverse events (AEs) in trials of maintenance immunosuppression in kidney transplantation.
Methods: We conducted a systematic review of published randomized controlled trials of maintenance immunosuppression following kidney transplantation in the Cochrane Kidney and Transplant Register (January 2003-December 2015). Appraisal against the 23-item harms extension of the Consolidated Standards of Reporting Trials statement was conducted.
Results: Of 233 trials, 163 (69%) reported at least one AE. Only 17 (10%) provided definitions or justified the AEs, 13 (8%) described methods and 27 (17%) measured severity. Forty AE types were reported, with gastrointestinal being the most common [116 (71%)]. The frequency of reporting did not reflect known drug side-effect profiles. For example, of 90 calcineurin inhibitor trials, only 22% reported tremors, 3% paresthesia and none anxiety, aggression or mood swings. Trials that reported at least one adverse effect were more likely to be industry funded {adjusted odds ratio [OR] 7.6 [95% confidence interval (CI) 3.4-17.1]}, multicenter [OR 5.9 (95% CI 1.7-18.7)] and with follow-up time <24 months [OR 3.7 (95% CI 1.4-10.2)].
Conclusions: AEs in kidney transplant immunosuppression trials appear to be selectively reported and may be unreliable for clinical decisions. Adherence to the Consolidated Standards of Reporting Trials harms extension should be mandatory to ensure transparent reporting of AEs that are important to patients and clinicians.

PMID: 29059401 [PubMed - indexed for MEDLINE]

Physicians' and pharmacists' perceptions on real-time drug utilization review system: a nationwide survey.

Int J Qual Health Care. 2017 Oct 01;29(5):634-641

Authors: Lee SM, Lee SO, Kim DS

Abstract
Objective: To identify healthcare providers' experience and satisfaction for the drug utilization review (DUR) system, their impact on prescription changes following alerts, and difficulties experienced in the system by surveying primary healthcare centers and pharmacies.
Design: A cross-sectional nationwide survey.
Setting and participants: Approximately 2000 institutions were selected for the survey by a simple random sampling of nationwide primary healthcare centers and community pharmacy approximately practices, and 358 replied.
Main outcomes measures: The questionnaire included questions on experience and recognition of DUR alerts, personal attitude and respondents' biographical information. Space was included for respondents to suggest improvements of the DUR system.
Results: The DUR system scored 71.5 out of 100 points for satisfaction by physicians and pharmacists, who reported that the alerts prevent medication-related errors; most respondents (96.6%) received the alerts. Several respondents (10.9%) replied that they prescribe or dispense prescriptions as they are without following the alerts. Physicians (adjusted odds ratio, 8.334; 95% confidence interval, 3.449-20.139) are more likely to change the prescription than pharmacists and persons with alert experience (4.605; 1.080-19.638). However, current practice in metropolitan areas (0.478; 0.228-1.000) and frequent alerts regarding co-administration incompatibilities within prescriptions (0.135; 0.031-0.589) negatively influence adherence to DUR alerts.
Conclusions: Although most surveyed physicians and pharmacists receive the alerts, some do not or reported that they would not follow the alerts. To increase adherence, the DUR system should be improved to ensure a preferential and intensive approach to detecting potentially high-risk drug combinations.

PMID: 28992160 [PubMed - indexed for MEDLINE]

[Research and application of hepatotoxicity evaluation technique of traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi. 2017 Jan;42(1):41-48

Authors: Song J, Zhong RL, Xia Z, Wu H, Zhong QX, Zhang ZH, Wei YJ, Shi ZQ, Feng L, Jia XB

Abstract
The safety of traditional Chinese medicine (TCM) has received the widespread attention in recent years. Hepatotoxicity of TCM is one of the key problems of the safety of TCM. This article summarized research progress and application prospect in the mechanism of TCM hepatotoxicity, biomarkers, toxic omics database, prevention of hepatotoxicity of the liver cell lines, subcellular fraction, three-dimensional cultivation models, the model animals, aiming to provide theoretical basis for TCM toxicity evaluation and technical guidelines, thus promoting the development of TCM toxicity studies. Hope for Chinese medicine liver toxicity evaluation method provides the theoretical foundation and technical guidelines, promote the development and improvement of TCM liver toxicity research system.

PMID: 28945023 [PubMed - indexed for MEDLINE]

[Expert consensus on the design and implementation of clinical safety centralized monitoring study of Chinese medical injection].

Zhongguo Zhong Yao Za Zhi. 2017 Jan;42(1):6-9

Authors: Zhang JH, Ren JT, Hu JQ, Xie YM, Song HB, Zhu MJ, Gao R, Wang Z, Zheng WK, Li XL, Jiang M, Huang YH, Lu F, He LY, Lian WX, Yang ZQ, Yuan WA, Hu SY, Wang BH, Wang WL, Ren DQ, Zhang BL, Clinical Pharmacology Committee of the China Association of Chinese Medicine, Clinical Curative Effect Evaluation Committee of the World Federation of Chinese Medicine Societies

Abstract
Along with the increase of clinical application, the safety of traditional Chinese medicine gained more and more attentions. In particular, the safety evaluation of Chinese medical injections has become a mandatory task should be completed by pharmaceutical companies under the supervision of China Food and Drug Administration(CFDA). Due to the weak foundation of previous studies, the safety issues of Chinese medical injections have not been fully understood, and lack of scientific and rational risk management programs. Clinical safety centralized monitoring(CSCM) is an important method for post-market safety evaluation of Chinese medicine. Due to the lack of appropriate norms and procedures, the quality of similar research is uneven, and the results vary. Combined with practical experience with experts' suggestions, we developed this expert consensus on the design and implementation of CSCM from three stages (design, implementation and report) with 20 technical points, which will provide technical support for future CSCM studies.

PMID: 28945018 [PubMed - indexed for MEDLINE]

Germline genetic variants with implications for disease risk and therapeutic outcomes.

Physiol Genomics. 2017 Oct 01;49(10):567-581

Authors: Pasternak AL, Ward KM, Luzum JA, Ellingrod VL, Hertz DL

Abstract
Genetic testing has multiple clinical applications including disease risk assessment, diagnosis, and pharmacogenomics. Pharmacogenomics can be utilized to predict whether a pharmacologic therapy will be effective or to identify patients at risk for treatment-related toxicity. Although genetic tests are typically ordered for a distinct clinical purpose, the genetic variants that are found may have additional implications for either disease or pharmacology. This review will address multiple examples of germline genetic variants that are informative for both disease and pharmacogenomics. The discussed relationships are diverse. Some of the agents are targeted for the disease-causing genetic variant, while others, although not targeted therapies, have implications for the disease they are used to treat. It is also possible that the disease implications of a genetic variant are unrelated to the pharmacogenomic implications. Some of these examples are considered clinically actionable pharmacogenes, with evidence-based, pharmacologic treatment recommendations, while others are still investigative as areas for additional research. It is important that clinicians are aware of both the disease and pharmacogenomic associations of these germline genetic variants to ensure patients are receiving comprehensive personalized care.

PMID: 28887371 [PubMed - indexed for MEDLINE]