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Chinese Journal of Traumatology =... Apr 2019The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint...
The clinical treatment of joint contracture due to immobilization remains difficult. The pathological changes of muscle tissue caused by immobilization-induced joint contracture include disuse skeletal muscle atrophy and skeletal muscle tissue fibrosis. The proteolytic pathways involved in disuse muscle atrophy include the ubiquitin-proteasome-dependent pathway, caspase system pathway, matrix metalloproteinase pathway, Ca-dependent pathway and autophagy-lysosomal pathway. The important biological processes involved in skeletal muscle fibrosis include intermuscular connective tissue thickening caused by transforming growth factor-β1 and an anaerobic environment within the skeletal muscle leading to the induction of hypoxia-inducible factor-1α. This article reviews the progress made in understanding the pathological processes involved in immobilization-induced muscle contracture and the currently available treatments. Understanding the mechanisms involved in immobilization-induced contracture of muscle tissue should facilitate the development of more effective treatment measures for the different mechanisms in the future.
Topics: Atrophy; Autophagy; Calcium; Caspases; Connective Tissue; Contracture; Fibrosis; Humans; Immobilization; Joints; Lysosomes; Matrix Metalloproteinases; Muscle, Skeletal; Proteasome Endopeptidase Complex; Proteolysis; Signal Transduction; Transforming Growth Factor beta1; Ubiquitin
PubMed: 30928194
DOI: 10.1016/j.cjtee.2019.02.001 -
Phytomedicine : International Journal... Apr 2019Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with...
BACKGROUND
Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems.
PURPOSE
Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin.
STUDY DESIGN AND METHODS
This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation.
RESULTS
The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies.
CONCLUSION
Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Biological Products; Cyclooxygenase 2; Disease Models, Animal; Humans; Inflammation; Inflammation Mediators; Molecular Targeted Therapy; NF-kappa B; Terpenes; Tumor Necrosis Factor-alpha
PubMed: 30668316
DOI: 10.1016/j.phymed.2018.10.028 -
Gene Feb 2019The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The roles of cyclooxygenase-2 (COX2) -765G > C (rs20417) and -1195G > A (rs689466) polymorphisms in gastric cancer were intensively analyzed, but the results of these studies were inconsistent. We conducted a meta-analysis and trial sequential analysis to elucidate the associations between these two COX2 polymorphisms and gastric cancer risk.
METHODS
Eligible studies were searched in PubMed, Embase, Cochrane library databases, China National Knowledge Infrastructure, Vip, and Wanfang databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the genetic correlation between COX2 polymorphisms and gastric cancer susceptibility in five genetic models. Trial sequential analysis (TSA) was conducted to estimate whether the evidence of the results is sufficient. Furthermore, their interactions with Helicobacter pylori (H. pylori) or smoking in gastric cancer were also assessed using a case-only method.
RESULTS
The COX2 gene -765G > C polymorphism showed no significant association with gastric cancer susceptibility under all the five genetic models (take the allelic model for example: OR = 1.41, 95% CI: 0.95-2.09) in total analysis, and the stratification analysis by ethnicity indicated a similar association in Caucasian group under four genetic models (allelic model, dominant model, homozygous model, and heterozygous model). But in the subgroup of the Asian population, the -765G > C polymorphism was significantly associated with gastric cancer risk under the same contrast. The COX2 -1195G > A polymorphism showed significant correlation with gastric cancer susceptibility in total analysis, and stratification analysis by ethnicity also revealed a similar association in both Asian and Caucasian groups under the same contrast. Moreover, TSA confirmed such associations. Both H. pylori infection and cigarette smoking interacted with -765 C allele in gastric cancer (OR = 3.79, 95% CI: 1.15-12.43 and OR = 2.48, 95% CI: 1.38-4.48, respectively), but not in -1195 A allele (OR = 1.96, 95% CI: 0.62-6.21, and OR = 1.24, 95% CI: 0.93-1.64, respectively).
CONCLUSIONS
COX2 -765G > C polymorphism may serve as a genetic biomarker of gastric cancer in Asians, but not in Caucasians. COX2 -1195G > A polymorphism may serve as a genetic biomarker of gastric cancer in both Asians and Caucasians. The -765G > C, rather than -1195G > A polymorphism interacted with H. pylori infection or cigarette smoking to increase gastric cancer risk.
Topics: Alleles; Cyclooxygenase 2; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Odds Ratio; Polymorphism, Single Nucleotide; Publication Bias; Smoking; Stomach Neoplasms
PubMed: 30391440
DOI: 10.1016/j.gene.2018.10.077 -
Medicina Oral, Patologia Oral Y Cirugia... Nov 2018This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
Preemptive analgesia-related gene and protein expression in third molar surgeries under non steroidal anti-inflammatory drug protocols: A PROSPERO-registered systematic review of clinical studies.
BACKGROUND
This study aimed to review trans lational studies focusing on third molar removal surgeries through a systematic analytical approach.
MATERIAL AND METHODS
A PROSPERO-registered systematic review (CRD42017060455) was conducted following the PRISMA statement to summarize current knowledge on gene expression in third molar surgeries. A search was performed in PubMed's Medline and Scopus databases, without date or language restrictions, using the logical expression {[(Third molar) OR (preemptive) OR (cyclooxygenase inhibitors) OR (acute inflammation) AND (gene expression)]}.
RESULTS
All studies included in the analysis evaluated gene expression in a third molar extraction model, using the preemptive analgesia methodology in seven investigations. The sample analyzed was obtained from gingival tissue biopsy (n=4), blood (n=1), transudate (n=1) and gingival tissue biopsy/transudate (n=1). There were differences with respect to evaluated genes, drug protocol, sample studied, and method for evaluating gene expression.
CONCLUSIONS
Third molar surgeries were found to be associated with different COX-related gene expression patterns. Although inflammatory events following the surgical procedure are associated with COX isoforms, data from preemptive analgesia studies are scarce, especially from studies correlating gene expression and clinical parameters. In the future, from a clinical perspective, identifying the molecular targets of a drug based on individual gene expression may be helpful to delineate specific third molar, surgery-related, preemptive analgesia protocols.
Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Gene Expression; Humans; Molar, Third; Prostaglandin-Endoperoxide Synthases; Protein Biosynthesis
PubMed: 30341263
DOI: 10.4317/medoral.22576 -
Inflammation Research : Official... Jan 2019Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia...
BACKGROUND
Lyme disease or Lyme borreliosis (LB) is the commonest vector-borne disease in the North America. It is an inflammatory disease caused by the bacterium Borrelia burgdorferi. The role of the inflammatory processes mediated by prostaglandins (PGs), thromboxanes and leukotrienes (LTs) in LB severity and symptoms resolution is yet to be elucidated.
OBJECTIVES
We aim to systematically review and evaluate the role of PGs and related lipid mediators in the induction and resolution of inflammation in LB.
METHODS
We conducted a comprehensive search in PubMed, Ovid MEDLINE(R), Embase and Embase Classic to identify cell-culture, animal and human studies reporting the changes in PGs and related lipid mediators of inflammation during the course of LB.
RESULTS
We identified 18 studies to be included into this systematic review. The selected reports consisted of seven cell-culture studies, seven animal studies, and four human studies (from three patient populations). Results from cell-culture and animal studies suggest that PGs and other lipid mediators of inflammation are elevated in LB and may contribute to disease development. The limited number of human studies showed that subjects with Lyme meningitis, Lyme arthritis (LA) and antibiotic-refractory LA had increased levels of an array of PGs and lipid mediators (e.g., LTB 8-isoPGF, and phospholipases A activity). Levels of these markers were significantly reduced following the treatment with antibiotics or non-steroidal anti-inflammatory drugs.
CONCLUSION
Dysregulation of prostaglandins and related lipid mediators may play a role in the etiology of LB and persistence of inflammation that may lead to long-term complications. Further investigation into the precise levels of a wide range of PGs and related factors is critical as it may propose novel markers that can be used for early diagnosis.
Topics: Animals; Biomarkers; Humans; Lyme Disease; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Severity of Illness Index
PubMed: 30121835
DOI: 10.1007/s00011-018-1180-5 -
International Journal of Surgery... Mar 2018Cystic echinococcosis (CE) represents an increasing public health concern in many parts of the world, including the Middle East. The present study is the first... (Meta-Analysis)
Meta-Analysis Review
Cystic echinococcosis (CE) represents an increasing public health concern in many parts of the world, including the Middle East. The present study is the first systematic review and meta-analysis to assess the seroprevalence rate and population genetic structure of human CE in the eastern Mediterranean region. To estimate the population genetic structure, Echinococcus sequences of the cytochrome oxidase subunit 1 (cox1) gene isolated from countries from this geographical area were retrieved from the GenBank database. An electronic search for articles from 1990 until 2015 was performed using databases PubMed, ScienceDirect, and Scopus. A total of 53 articles reporting on CE seroprevalence and genotyping data met our eligibility criteria and were included in a meta-analysis. The overall CE seroprevalence rates in the general population and in individuals at high risk of infection were estimated using the random-effect model at 7.4% (95% CI = 4.8-10.6) and 10.7% (95% CI = 7.6-14.3), respectively. Risk factors including age group (P < 0.001), dog ownership (P = 0.03), residence area (P < 0.001), and educational level (P = 0.04) showed a statistically significant association with CE seroprevalence. A pairwise fixation index (Fst), used as an estimation of gene flow, suggested a moderate level of genetic differentiation between members of the E. granulosus sensu stricto (G1-G3) complex from Iranian and Turkish metapopulations (Fst = 0.171). The finding of common haplotypes may represent an ancestral transfer of alleles among populations probably during the early stages of animal domestication. The high CE seroprevalence rates found highlight the necessity of implementing appropriate public education for preventive and control strategies, particularly in individuals at high risk of infection; furthermore, our genetic findings reveal novel molecular data concerning microevolutionary events of Echinococcus isolates among Middle East countries.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Asian People; Cyclooxygenase 1; Dogs; Echinococcosis; Female; Genetic Variation; Genetics, Population; Genotype; Haplotypes; Humans; Iran; Male; Middle Aged; Middle East; Risk Factors; Seroepidemiologic Studies; Turkey; Young Adult
PubMed: 29367032
DOI: 10.1016/j.ijsu.2018.01.025 -
The Journal of Antimicrobial... Mar 2018Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance.
METHODS
This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information.
RESULTS
Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent.
CONCLUSIONS
Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation.
Topics: Atovaquone; Drug Combinations; Drug Resistance, Multiple; Drug Therapy, Combination; Electron Transport Complex III; Humans; Malaria, Falciparum; Malaria, Vivax; Mutation; Plasmodium falciparum; Proguanil; Travel; Treatment Failure
PubMed: 29237012
DOI: 10.1093/jac/dkx431 -
The Cochrane Database of Systematic... Dec 2017Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in October 2015.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (16 May 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5), MEDLINE (1949 to 16 May 2017), Embase (1980 to 16 May 2017), CINAHL (1982 to 16 May 2017), AMED (1985 to 16 May 2017), and 11 Chinese databases (16 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the quality of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous.Recurrent strokeThree studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-quality evidence).Adverse eventsEvidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence interval and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-quality evidence).Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-quality evidence that PPAR-γ agonists led to fewer events (data not meta-analysed).Vascular eventsPeroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-quality evidence).Other outcomesOne study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
Topics: Cardiovascular Diseases; Carotid Artery Diseases; Humans; Hypoglycemic Agents; Insulin Resistance; Ischemic Attack, Transient; Myocardial Infarction; PPAR gamma; Pioglitazone; Proteasome Endopeptidase Complex; Randomized Controlled Trials as Topic; Recurrence; Rosiglitazone; Secondary Prevention; Stroke; Thiazolidinediones; Ubiquitin
PubMed: 29197071
DOI: 10.1002/14651858.CD010693.pub4 -
American Journal of Reproductive... Feb 2018Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory... (Review)
Review
Parturition at term is characterized by inflammatory overload in both feto-maternal tissues. Despite the large number of individual studies on changes in inflammatory biomarkers linked to labor, a comprehensive profile of them in each of the uterine compartments is not available to better understand their mechanistic contributions to labor. This systematic review investigated the pro- and anti-inflammatory biomarkers reported in intra-uterine tissues (amnion, chorion, decidua, placenta, and myometrium) at term labor. We conducted a systematic review of studies on pro- and anti-inflammatory biomarkers (mRNA and/or protein) reported in feto-maternal tissues during normal human term labor, published in English (1980-2016), in 3 electronic data bases. From a total of 3712 citations, 172 were included for final review. Each tissue expresses a unique set of biomarkers at the time of term labor, but there is significant overlap between tissues. All tissues had IL-6, IL-8, IL-1β, COX-2, PGE-2, TNF-α, and hCAP18 in common at term labor. Common and unique inflammatory biomarkers are expressed in various feto-maternal compartments at term labor. Increase in pro-inflammatory markers in all gestational tissue signifies their harmonious functional role in promoting labor. Anti-inflammatory markers at term labor are hardly reported.
Topics: Animals; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Cyclooxygenase 2; Female; Humans; Inflammation; Inflammation Mediators; Metalloporphyrins; Parturition; Pregnancy; Uterus
PubMed: 29076197
DOI: 10.1111/aji.12776 -
Journal of Clinical Neuroscience :... Oct 2017Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene... (Review)
Review
BACKGROUND
Cervical spondylotic myelopathy (CSM) is a degenerative disorder of the neck. Recent studies have reported the roles of single nucleotide polymorphisms and abnormal gene expression in the etiology and development of CSM. However, a systemic review of these findings is currently unavailable.
METHODS
A systemic review of genetic factors of CSM was conducted through searching PubMed and EMbase databases. A total of 9 studies were included in this study, which included 8 genes: brain derived neurotrophic factor (BDNF), osteopontin (OPN), bone morphogenic protein (BMP) 4, collagen IX, vitamin D receptor (VDR), apolipoprotein E (ApoE), hypoxia-inducible factor α (HIF-1α), and cyclooxygenase 2 (COX-2).
RESULTS
The polymorphisms of 6 genes (OPN, BMP-4, collagen IX, VDR, HIF-1α) showed significant association with the susceptibility to or risk of CSM. The polymorphisms of 3 genes (BMP-4, ApoE4, HIF-1α) were significantly associated with the postoperative outcome. The polymorphism of BDNF, VDR, and expression of COX-2 were associated with the severity of disease.
CONCLUSION
This review demonstrates that 8 genes were associated with CSM although there is no repeated study. This review also suggests that large scale and high quality studies are needed to provide more reliable evidence for future evaluation.
Topics: Humans; Apolipoprotein E4; Brain-Derived Neurotrophic Factor; Cyclooxygenase 2; Genetic Predisposition to Disease; Neurosurgical Procedures; Osteopontin; Polymorphism, Single Nucleotide; Postoperative Complications; Receptors, Calcitriol; Spondylosis
PubMed: 28734792
DOI: 10.1016/j.jocn.2017.06.043