Animal Studies Research Articles

Preclinical evidence and possible mechanisms of cardioprotective effects of resveratrol in diabetic cardiomyopathy: a systematic review and meta-analysis

Abstract Introduction Diabetic cardiomyopathy (DCM) is a significant complication of diabetes, characterized primarily by the development of heart failure in individuals with diabetes. Numerous animal studies have indicated that resveratrol enhances cardiac function in diabetic cardiomyopathy; however, its reliability and underlying mechanism remain unclear. This study aims to assess the cardioprotective effects of resveratrol on DCM and explore its potential mechanism. Methods We searched PubMed, EMBASE, WOS, Cochrane Library, CNKI, CBM, Chinese VIP, and Wan Fang Database until March 31st, 2024, without language restrictions. Continuous outcome measures were analyzed using weighted mean difference or standardized mean difference, and heterogeneity was assessed with I2. The risk of bias in animal experiments was evaluated using the SYRCLE tool, and evidence reliability was determined with the GRADE tool. All data were analyzed using Review Manager 5.4.1 and Stata 17. This study has been registered on the PROSPERO (CRD42024523944). Results A total of 18 studies meeting the criteria were identified. The analysis revealed that the resveratrol intervention group exhibited significant improvements in LVEF (WMD = 17.88), LVFS (WMD = 8.77), HW/BW (SMD=-2.92), SOD (SMD = 4.53), and MDA (SMD=-5.07) compared to the control group. The GRADE grading assessment indicated moderate certainty for LVEF, HW/BW, and MDA, while certainty for other factors was considered low. Conclusion Our research suggests that resveratrol may protect cardiac function in DCM through anti-inflammatory and anti-oxidative stress effects. However, these findings are based on preclinical data, and further extensive trials are needed to confirm their effectiveness and safety before clinical application.

Effect of photobiomodulation and corticopuncture methods on tooth displacement and gene expression: animal study.

The aim of this study was to evaluate the expression levels of vascular endothelial growth factor (VEGF), Peroxiredoxin 1 (PRX1), glucose transporter 1 (GLUT1) and type I collagen (COL1) and the rate of tooth movement comparing 3 accelerated tooth movement (ATM) methods: Corticopuncture (CP), photobiomodulation (PBM) and the combined technique (CP + PBM) on days 1, 3, 7 and 14. Orthodontic tooth movement was induced in 24 male Wistar rats. CP procedure included three perforations: two in the palate and one mesial to the molars. GaAlAs diode laser irradiation was performed on days 0, 2, 4 and 6, totaling 4 irradiations. 14 days (810nm, 100 mW, 15s). Gingival tissue was collected from the cervical area of both first molars and qPCR was performed to isolate and quantify mRNA levels. All ATM groups showed increased tooth displacement compared to control after 14 days (20% for PBM; 40% for CP and 60% for CP + PBM). PBM showed higher VEGF expression on days 1,3 and 7 followed by CP and CP + PBM. PRX1 levels increased on days 1 and 3 in PBM and CP + PBM. GLUT1 increased on day 3 in all groups. No difference was found on levels of VEGF, PRX1 and GLUT1 among the groups on day 14, except for COL1 which increased significantly in PBM group. All ATM methods showed higher expression of all of VEGF, PRX1, GLUT1, COL1 than control group. PBM and CP + PBM groups had more expression related to angiogenesis, glucose uptake, oxidative stress and collagen synthesis.

Effectiveness of autologous fat graft and methylprednisolone as single and combination therapy in the prevention of epidural fibrosis

Objectives: Epidural fibrosis is a common complication following laminectomy, contributing to failed back surgery syndrome characterized by back pain and radiculopathy. Despite ongoing research, no consensus exists on the best method to prevent epidural fibrosis. This animal study aimed to compare the effectiveness of autologous fat grafts and methylprednisolone as single and combination therapies in preventing epidural fibrosis. Methods: Four groups of rats, each containing 7, underwent different treatments post-lumbar laminectomy: A control group, a group receiving methylprednisolone in the epidural space, a group receiving an autologous fat graft, and a group receiving both methylprednisolone and an autologous fat graft. After 6 weeks, the formation of epidural fibrosis was evaluated through histopathological examination based on the classification. The degree of epidural fibrosis was analyzed. Results: The autologous fat graft group exhibited the lowest degree of fibrosis (Grade 1). Comparisons between this group and the others showed a significant difference (P < 0.05). No significant difference was observed between the control, methylprednisolone, and combination groups (P > 0.05). Conclusion: The study demonstrated a significant reduction in histological epidural fibrosis using autologous fat grafts compared to methylprednisolone and their combination in animal models. Histological analysis indicated that autologous fat grafts resulted in a lower degree of fibrosis following laminectomy.

Multimodal evaluation of network activity and optogenetic interventions in human hippocampal slices.

Seizures are made up of the coordinated activity of networks of neurons, suggesting that control of neurons in the pathologic circuits of epilepsy could allow for control of the disease. Optogenetics has been effective at stopping seizure-like activity in non-human disease models by increasing inhibitory tone or decreasing excitation, although this effect has not been shown in human brain tissue. Many of the genetic means for achieving channelrhodopsin expression in non-human models are not possible in humans, and vector-mediated methods are susceptible to species-specific tropism that may affect translational potential. Here we demonstrate adeno-associated virus-mediated, optogenetic reductions in network firing rates of human hippocampal slices recorded on high-density microelectrode arrays under several hyperactivity-provoking conditions. This platform can serve to bridge the gap between human and animal studies by exploring genetic interventions on network activity in human brain tissue.

Research on the TSPAN6 regulating the secretion of ADSCs-Exos through syntenin-1 and promoting wound healing.

Exosomes (Exos) from adipose-derived stem cells (ADSCs) have a high inclusion content and low immunogenicity, which helps to control inflammation and accelerate the healing of wounds. Unfortunately, the yield of exosomes is poor, which raises the expense and lengthens the treatment period in addition to impairing exosomes' therapeutic impact. Thus, one of the key problems that needs to be resolved in the current exosome study is increasing the exosome yield. Tetraspanin-6 (TSPAN6) overexpression and knockdown models of ADSCs were constructed to determine the number of exosomes secreted by each group of cells as well as the number of multivesicular bodies (MVBs) and intraluminal vesicles (ILVs) within the cells. Subsequently, the binding region of the interaction between TSPAN6 and syntenin-1 was identified using the yeast two-hybrid assay, and the interaction itself was identified by immunoprecipitation. Finally, cellular and animal studies were conducted to investigate the role of each class of exosomes. When compared to the control group, the number of intracellular MVBs and ILVs was significantly larger, and the number of ADSCsTSPAN6+-Exos was more than three times higher. However, TSPAN6's ability to stimulate exosome secretion was reduced as a result of syntenin-1 knockdown. Additional yeast two-hybrid assay demonstrated that the critical structures for their interaction were the N-terminal, Postsynaptic density protein 95/Discs large protein/Zonula occludens 1 (PDZ1), and PDZ2 domains of syntenin-1, and the C-terminal of TSPAN6. In animal trials, the wound healing rate was best in the ADSCsTSPAN6+-Exos group, while cellular experiments demonstrated that ADSCsTSPAN6+-Exos better enhanced the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs). TSPAN6 stimulates exosome secretion and formation, as well as the creation of MVBs and ILVs in ADSCs. Syntenin-1 is essential for TSPAN6's stimulation of ADSCs-Exos secretion. Furthermore, ADSCsTSPAN6+-Exos has a greater ability to support wound healing, angiogenesis, and the proliferation and migration of a variety of cells.

Beyond the Scale: Exploring the Endocannabinoid System's Impact on Obesity.

This review explores the role of the endocannabinoid system (ECS) in regulating energy balance, food intake, and metabolism, with a focus on how ECS dysregulation contributes to obesity. The goal is to provide insights into the mechanisms underlying obesity and its associated metabolic disorders. Recent research indicates that the ECS significantly influences food intake, fat storage, insulin sensitivity, and inflammation, all of which are central to the development and progression of obesity. New research areas include the interaction between the ECS and gut microbiota, circadian rhythms of the ECS, and the impact of genetic and epigenetic factors on ECS function. Interest in the therapeutic potential of targeting the ECS has grown, with earlier treatments like CB1 receptor antagonists showing mixed results in efficacy and safety. Evidence from both animal and human studies highlight the impact of elevated levels of the endocannabinoids anandamide and 2-AG on food intake, insulin resistance, visceral fat accumulation, and metabolic disturbances associated with obesity. The review explores the interaction between the ECS and other physiological systems, including gut-brain communication, circadian rhythms, as well as leptin and ghrelin signaling. Additionally, genetic and epigenetic factors influencing ECS function are examined, emphasizing their contribution to obesity susceptibility. While therapeutic approaches targeting the ECS, particularly CB1 receptor antagonism, have shown potential in managing obesity, the review acknowledges the challenges posed by central nervous system side effects in earlier treatments like rimonabant. However, recent advancements in peripherally restricted CB1 antagonists offer renewed hope for safer and more effective obesity treatments. The review concludes by addressing future research directions and therapeutic strategies to combat this global health challenge.

Evaluation of mesenchymal stem cells as an in vitro model for inherited retinal diseases

Retinal pathologies are major causes of vision impairment and blindness in humans, and inherited retinal diseases (IRDs), such as retinitis pigmentosa, Leber congenital amaurosis, and Stargardt disease, greatly contribute to this problem. In vitro disease modeling can be used for understanding the development of pathology and for screening therapeutic pharmaceutical compounds. In the preclinical research phase, in vitro models complement in vivo models by reducing animal studies, decreasing costs, and shortening research timelines. Additionally, animal models may not always accurately replicate the human disease phenotype. This review examines the types of cells that can be used to create in vitro IRD models, including retina-specific cell lines, primary retinal cells, induced pluripotent stem cells (iPSCs), and more. Special attention is given to mesenchymal stem cells (MSCs), which are characterized by various isolation sources, relative ease of isolation, and straightforward differentiation. MSCs derived from bone marrow (BM), adipose tissue (AT), dental tissue (DT), umbilical cord (UC), and other sources can differentiate into retinal cells, including photoreceptor cells and retinal pigment epithelial (RPE) cells, dysfunction of which is most commonly associated with IRDs. Subsequent differentiation of MSCs into retinal cells can be carried out via various methods: culturing in induction media supplemented with certain growth factors, co-culturing with retinal cells or in their conditioned media, or regulating gene expression with viral vector-delivered transcription factors (TFs) or microRNAs (miRNAs). Compared to the popular iPSCs, for example, MSC-based models are significantly cheaper and faster to obtain, making them more feasible for large-scale drug screening. Nevertheless, the existing differentiation methods need further optimization for this promising platform to receive the success it deserves.

Multicellular 3D models to study myocardial ischemia–reperfusion injury

Coronary heart disease is a major global health threat, with acute myocardial ischemia–reperfusion injury (IRI) being a major contributor to myocardial damage following an ischemic event. IRI occurs when blood flow to ischemic tissues is restored and exacerbates the cellular damage caused by ischemia/hypoxia. Although animal studies investigating IRI have provided valuable insights, their translation into clinical outcomes has been limited, and translation into medical practice remains cumbersome. Recent advancements in engineered three-dimensional human in vitro models could offer a promising avenue to bridge the “therapeutic valley of death” from bench to bedside, enhancing the understanding of IRI pathology. This review summarizes the current state-of-the-art cardiovascular 3D models, including spheroids, organoids, engineered cardiac microtissues, and organ-on-a-chip systems. We provide an overview of their advantages and limitations in the context of IRI, with a particular emphasis on the crucial roles of cell–cell communication and the multi-omics approaches to enhance our understanding of the pathophysiological processes involved in IRI and its treatment. Finally, we discuss currently available multicellular human 3D models of IRI.

Monitoring Bottlenose Dolphin (Tursiops truncatus) Welfare During a Functional Neuroimaging Study

The development of non-invasive methods to study brain structure and function has enabled a flowering of cognitive neuroscience in humans and nonhuman species. Herein, we describe the development of protocols for functional magnetic resonance imaging (fMRI) of a bottlenose dolphin (Tursiops truncatus), including protocols to monitor the health and welfare of the subject over the course of our five-year study. A Welfare Control Plan (WCP) was designed to monitor, enhance, and protect our subject’s welfare throughout the course of the study. The WCP was developed so our team of marine mammal veterinarians, trainers, and researchers could (1) identify study procedures that might negatively impact the individual’s welfare and propose measures to mitigate them, (2) define and implement protocols for monitoring the individual’s welfare throughout the study, and (3) determine the study’s temporary or final endpoints. Overall, behavioral, physiological, and health welfare indicators showed that the dolphin’s quality of life was not negatively impacted by participating in our functional neuroimaging study. Our study provides an example of how innovative, ambitious, and logistically complex animal studies can successfully be performed while protecting the welfare of participating animals through adequate planning, enough human and economic resources, and full human/institutional commitment to animal welfare.

Noncanonical Amino Acid Incorporation in Animals and Animal Cells.

Noncanonical amino acids (ncAAs) are synthetic building blocks that, when incorporated into proteins, confer novel functions and enable precise control over biological processes. These small yet powerful tools offer unprecedented opportunities to investigate and manipulate various complex life forms. In particular, ncAA incorporation technology has garnered significant attention in the study of animals and their constituent cells, which serve as invaluable model organisms for gaining insights into human physiology, genetics, and diseases. This review will provide a comprehensive discussion on the applications of ncAA incorporation technology in animals and animal cells, covering past achievements, current developments, and future perspectives.

Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease.

In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.

Long term links between maternal diet during pregnancy and offspring health.

The developmental origins of health and disease hypothesis propose that lifelong health is programmed during foetal development, in utero. The world's population is ageing due to increased longevity but expanding morbidity and the associated burden on health systems around the planet, are associated with this. Consequently, resources are strained and spent largely on treating patients rather than preventing chronic diseases at their source. Research on early life exposures, starting in the womb, is needed to identify new potential biomarkers linked with the development of chronic diseases during adulthood. Evidence from maternal-offspring cohorts investigating associations between pregnancy exposures and childhood metabolic health is reviewed (The GUSTO study in Singapore, the Copenhagen Prospective Studies on Asthma in Childhood, a mother-child cohort in rural Gambia, the MINIMat study in Bangladesh, The Iodine Status in Pregnancy and Offspring Health Cohort in China, the OBESO cohort in Mexico, the Pune Nutrition study in India, The Reus-Tarragona Birth Cohort study in Spain). Collectively, evidence from prospective observational studies, randomised controlled trials and animal studies, supports the hypothesis that maternal diet, lifestyle and nutritional status during pregnancy are associated with childhood metabolic health in the offspring. However, the evidence is scant and further research is needed.

Visseral Lipectomy Improves Metabolic Syndrome Parameters and Adipokines in a Rat Model of Metabolic Syndrome Induced by Monosodium Glutamate.

Metabolic syndrome (MetS) includes abdominal obesity, hypertension, insulin resistance, and dyslipidemia. Research has indicated that reducing excess visceral fat has positive effects on inflammation and insulin resistance. We examined whether visceral lipectomy modifies the effects of MetS parameters and adipocytokine levels. Each group included 15 newborn male rats: control+sham (C+S), metabolic syndrome+sham (MetS+S), and metabolic syndrome+visceral lipectomy (MetS+VL). On postnatal days 0, 2, 4, 6, 8, and 10, subcutaneous injections of monosodium glutamate (MSG) (4g/mg) were administered to induce MetS. The control group received saline injection. The rats underwent sham surgery or lipectomy on the 120th day of life. Two months post-surgery, tests were performed to check lipid and insulin levels as well as the Lee index, HOMA-IR, serum adiponectin (ADP), resistin, interleukin-6 (IL6), leptin, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) levels. These findings showed that the Lee index (p = 0.001), insulin resistance (p = 0.002), and hyperinsulinemia (p = 0.009) were significantly improved in the MetS+VL group compared to those in the MetS+S group. The lipid profile was unaffected by visceral lipectomy. Furthermore, visceral lipectomy normalized MetS-induced adipokine imbalance. The decrease in the Lee index and improvement in hyperinsulinemia suggest that visceral lipectomy may benefit impaired glucose metabolism. Although visceral lipectomy has no apparent effect on the lipid profile, positive effects on adipokine levels by reducing various inflammatory markers including resistin, IL6, leptin, TNF-α, and CRP. These findings indicate that visceral lipectomy may have therapeutic potential for MetS. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Assessment the bioactivity of zinc oxid eugenol sealer after the addition of different concentrations of nano hydroxyapatite-tyrosine amino acid

Aim: Zinc oxide eugenol sealer has been used till now in endodontic obturation. However, despite many improvements in its formula, it still does not have, the essential root canal sealer’s properties which is the apatite forming ability. The aim of the present study is to assess the effect of the incorporation of nano Hydroxyapatite- tyrosine amino acid at different concentrations in the zinc oxide eugenol sealer formula in terms of bioactivity analysis. Methods: The nano hydroxy apatite-tyrosine amino acid was incorporated into the original zinc oxide eugenol (endosell) at different concentrations starting from (10 – 20)%. The chemical changes in zinc oxide eugenol before and after addition were characterized using FTIR and XRD. The setting time test was done according to ADA specification no. 57. The bioactivity analysis for the zinc oxide eugenol before and after the addition was evaluated according to ISO/FDIS 23317:2007(E) by using 28 days of storage in phosphate buffer saline, and then the hydroxyapatite precipitation and Ca/P ratio was evaluated using FESEM/EDX. Results: The FTIR and XRD confirmed the setting reaction occurrence among the (original ZOE, nHAP, and Tyr). The XRD and FESEM/EDX analyses confirmed the HAP precipitation on the ZOE sample surfaces after the addition of (nHAP-Tyr a.a) and this precipitation was increased with increased concentrations of additions. Conclusion: Incorporated (20) % of equal amounts of “nHA-Tyr a.a” can convert the ZOE to bioactive sealer as confirmed by XRD and FESEM/EDX. However, other characteristic analyses like Nuclear magnetic resonance, atomic force microscopy, and in vivo animal study were needed to further confirm the results.

Intermittent hypoxia training improves cerebral blood flow without cognitive impairment.

Brief exposure to intermittent hypoxia has been shown to potentially induce protective effects in the body. Animal studies suggest that intermittent hypoxia could increase cerebral blood flow and confer resistance to subsequent hypoxic-ischemic injury, yet clinical investigations are limited. This study aimed to evaluate the impact of a moderate short-term intermittent hypoxia protocol on cerebral blood flow and cognitive performance. Subjects who met the inclusion criteria were recruited to this study and randomized into the intermittent hypoxia group or the control group, which receives intermittent hypoxia training and sham-intermittent hypoxia training, respectively. Cerebral hemodynamics, cognitive performance, cerebral perfusion pressure, and oxygen saturation were assessed before and after the intervention. A total of 100 healthy participants were included in this study. Compared to the control group, the intermittent hypoxia group exhibited higher peak systolic blood flow velocity (108.64 ± 22.53 vs. 100.21 ± 19.06, p = 0.049) and cerebrovascular conduction index (0.74 ± 0.17 vs. 0.66 ± 0.21, p = 0.027), and lower cerebrovascular resistance index (1.41 ± 0.29 vs. 1.54 ± 0.36, p = 0.044) following intermittent hypoxia training. Additionally, within-group comparisons revealed that intermittent hypoxia training led to increased cerebral blood flow velocity, elevated cerebrovascular conductance index, and decreased cerebrovascular resistance index (p < 0.05). Other indicators including cognitive function, cerebral perfusion pressure, and oxygen saturation did not exhibit significant differences between groups. These findings revealed that intermittent hypoxia may represent a safe and effective strategy for improving cerebral blood flow.

Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent?

Purpose of review This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. Recent findings Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. Summary Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

Association of edentulism and obstructive sleep apnea: A systematic review.

Sleep apnea is a common and underdiagnosed sleep-related breathing disorder. This systematic review aimed to evaluate the scientific evidence regarding the association between obstructive sleep apnea (OSA) and edentulism. An electronic search was conducted through PubMed (MEDLINE), Scopus, and Cochrane Library, up to January 2024. A systematic approach was followed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement guidelines. The literature search intended to retrieve all relevant clinical studies about any possible association between OSA and edentulism. Only publications in the English language were selected, and animal studies, in vitro studies, case reports, case series, technique presentation articles, and expert opinions were excluded. A total of 23 studies met the inclusion criteria and were included in this systematic review. They were published between 1999 and 2023 and were all clinical studies. These studies examined a possible association between OSA and edentulism and all of them agreed on their positive relation. Tooth loss favors anatomic alterations that deteriorate breathing. The severity of OSA was related to the extent and duration of edentulism. Mean Apnea-Hypopnea Index (AHI) scores in edentulous patients were found to be two to three times higher in comparison to dentate individuals, although the statistical data about it are scarce. No agreement was reached, however, about the use of dentures during sleep time, since the data are controversial. The findings suggest that there is a plausible association between edentulism and OSA. Tooth loss impairs significant anatomic alterations and increases the risk for OSA. However, clinical data are limited and heterogeneous so more clinical studies should be encouraged for more robust conclusions.

BN SO63 - A systematic review of Hiatus Hernia classifications

Abstract Background Hiatus hernias (HH) are common, an important cause of symptoms, and a strong risk factor for complications and oesophageal dysplasia and adenocarcinoma. However, there is a lack of consensus as to how they should be classified. This has significant implications for benchmarking and standardising practice, as well as generating and answering research questions. The aim of this review was to systematically identify and appraise what classification systems have been described, and to identify any novel approaches to HH classifications and their association with treatment outcomes. Method We undertook a systematic review of the PubMed and EMBASE databases on the 17th January 2023. Inclusion criteria were any studies containing a HH classification described within adults. Exclusion criteria were studies not in English, animal studies and case reports. Results 847 articles were identified. 245 were included, with a further 9 studies identified that tested a novel approach to classifying HH against surgical outcomes. Most classification systems (64.9%) were anatomical, but with significant variation as regards stratification of size of the hernia, and its contents (primarily the proportion of herniated stomach). A small number of classifications described endoscopic, manometry, symptomatic and intra-operative classifications. There was considerable heterogeneity in the definitions used for larger HH. The quality of studies comparing classifications with outcomes was limited; however, some possible associations were reported based on anatomical and physiological parameters. Conclusion We found a wide range of HH classification systems. These were mainly anatomical and based on the traditional type I-IV system. Whilst the evidence is limited, it seems likely that other components (anatomical and physiological) may have utility in better classifying HH and guiding treatment, standardisation and research.

Does adjunctive phototherapy have better outcomes than adjunctive antibiotic therapy for the management of peri-implantitis?

Elsevier's Scopus, Web of Science and Pubmed through Medline identified 431 articles, which were reduced to 206 when duplicates were removed. 8 articles were screened, and 1 excluded after reading the full-text, leaving 7 studies. 6 of these were randomised controlled trials, and 1 a non-randomised controlled clinical trial. Studies selected were either blinded, double-blinded, split-mouth clinical studies, comparative or controlled clinical studies, or randomised controlled trials in humans. There were no limitations on year of publication or language of studies. Most studies had a control of mechanical debridement (MD) with adjuvant antibiotics; 1 was surgical therapy. The test group was MD with adjuvant phototherapy. Exclusions were in vitro reports, animal studies, treatment with sole laser therapy, treatment with no additional antimicrobial therapy alongside MD. Pre-prints, reviews, abstracts, opinion articles, editorials, case reports and case series were also excluded. Data were extracted electronically by a single author and a senior librarian from the 3 databases. Titles and abstracts of articles were screened by the author if they contained Medical Subject Headings either in free terms or with Boolean operators. Full text studies that met the inclusion criteria were included. Data were also searched manually in 6 journals. For missing or conflicting information, the author of the article was contacted for clarification. Data extracted were country of origin of article, study design, sample size, research groups, diagnostic criteria, frequency of intervention, follow-up visits, and outcome of parameters which included clinically: plaque index (PI), probing depth (PD), bleeding on probing (BOP) and radiographically: crestal bone loss (CBL). Additional data on lasers were also collected, although not all studies had complete data on this. RevMan was used for statistical analysis. Inconsistencies were evaluated using I2 value > 50% and Cochrane's Q test, with a P value < 0.05 considered. Standard Mean Differences (SMD) were calculated and Confidence Interval was set at 95%. A random effects model was used for each meta-analysis. PI had no statistical difference, with high heterogeneity. PD had no statistical difference, with no heterogeneity. BOP had a statistically significant difference and a high level of heterogeneity, favouring adjunctive phototherapy. MBL had statistically non-significant differences between control and test groups, and no heterogeneity. The findings from the systematic review differed from the meta-analysis, suggesting that application of adjuvant phototherapy was equally as effective as adjunctive antibiotic therapy in outcomes such as PI, PD, BOP and MBL. The meta-analysis found that implants treated with adjuvant phototherapy had superior outcomes in relation to BOP only.

The Role of Delta-Opioid Receptor in Mediating the Cardioprotective Effects of Morphine Preconditioning via the JAK2/STAT3 Pathway in a Failing Heart

BACKGROUND: Failing heart is more likely to suffer from myocardial ischemia/reperfusion (I/R) injury. This poses a great challenge for anesthesiologists in managing patients with heart failure during major surgery. Evidence from animal studies suggests that the delta-opioid receptor (DOR) contributes to alleviating acute myocardial injuries. However, little is known regarding the cardioprotective effects of cardiac DOR in patients with chronic heart failure. This study aimed to examine DOR expression in failing hearts and explore how DOR regulates the Janus kinase signal transducer and activator of the transcription-3 (JAK/STAT3) pathway to mediate morphine-induced cardio protection in heart failure. METHODS: We measured the DOR protein levels in human and rat heart tissues with chronic heart failure. To investigate the cardioprotective role of DOR, we administered the DOR-specific antagonist, naltrindole (NTD), and JAK2 inhibitor, AG490, before morphine preconditioning (MPC) in an isolated perfusion model of myocardial I/R injury in postinfarcted failing rat heart. We examined the infarct size, cardiac enzymes, cardiac function, cardiomyocyte apoptosis, apoptosis-related proteins, and STAT3 phosphorylation in the heart. RESULTS: The protein levels of DOR were significantly elevated in the myocardial tissues of humans and rats with chronic heart failure, by 1.4-fold (mean difference 0.41; 95% confidence interval [CI], 0.04–0.78; P = .032) and 2.3-fold (mean difference 1.26; 95% CI, 0.25–2.28; P = .009), respectively, compared to control tissues. Disease severity positively correlated with DOR expression (human: R2 = 0.316, P = .004; rat: R2 = 0.871, P = .021). Blocking DOR substantially reversed the cardioprotective effects of MPC in postinfarcted rat hearts, increasing the mean (standard deviation) percentage of infarct size from 15.0 (3.9)% to 30.8 (7.7)% (P &lt; .001). Similarly, AG490 inhibited MPC restoration of cardiomyocyte apoptosis (33.3 [4.2]% vs 16.6 [3.4]%; P &lt; .001). Both NTD and AG490 markedly suppressed STAT3 phosphorylation by 60.1% (mean difference 0.60; 95% CI, 0.27–0.93; P = .002) and 44.1% (mean difference 0.44; 95% CI, 0.06–0.83; P = .027), respectively, and also lowered the Bcl-2/Bax ratio by 85.5% (mean difference 0.86; 95% CI, 0.28–1.43; P = .006) and 68.2% (mean difference 0.68; 95% CI, 0.51–0.85; P &lt; .001) respectively in heart tissues at the end of reperfusion. CONCLUSIONS: DOR protein levels increased in failing hearts of both humans and rats. Blocking cardiac DOR selectively reduced morphine-induced cardio protection by inhibiting the JAK2/STAT3 pathway. These findings indicate that cardiac DOR is a potential therapeutic target for protecting against heart failure due to I/R injury.