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Background: Mediterranean diet may enhance cognitive function and delay the progression of Alzheimer's disease (AD). We conducted a systematic review to investigate the effect of oleocanthal (OC) from extra-virgin olive oil (EVOO) on amyloid-β (Aβ) burden in preclinical models of AD, considering the anti-inflammatory and neuroprotective effects of EVOO biophenols, which are key components of the Mediterranean dietary model., Methods: The literature was searched through six electronic databases until February 2023. Screening of 52 retrieved articles for inclusion criteria resulted in 7 preclinical reports evaluating the effect of an OC-supplemented diet on AD trajectories by means of Aβ load or clearance in affected models. Reports were appraised for risk of bias using the SYRCLE's RoB tool. A protocol was registered on PROSPERO., Results: Case control prevailed over the case-crossover design, and the geographical distribution was uniformly American. The study population mostly included 5xFAD, otherwise TgSwDI or wild-type C57BL/6 mouse models. We found a role of OC in reducing Aβ load in the hippocampal parenchyma and microvessels compared with controls. An increased cerebral clearance of Aβ through the bloodbrain barrier and a substantial improvement in metabolic and behavioral parameters were also reported in preclinical models under an OC-enriched diet. The risk of bias was shown to be moderate overall., Conclusion: Preclinical data are promising about the effects of OC from the Mediterranean diet's EVOO in relieving the burden of Aβ in AD; however, further evidence is needed to corroborate the efficacy of this biophenol and strengthen the speculated causal pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Bigles are novel formulation merging two phase of hydrogel and organogel revealing dual properties to release active agents based on their lipophilic or hydrophilic nature., Methods: A systematic search was conducted in PubMed, Scopus, and ISI Web of Science to find eligible studies evaluating the efficiency of bigels in drug release. 20 articles were included in the analysis based on the defined criteria., Results: The results indicated that several different natural materials were used for bigel making. Span (52.38%) and Sunflower oil (23.80%) were the most solvents used for organogel formation. Also, gelatin, agar, gums, and other types of biopolymer were used as hydroglators. Most research (33.33%) focused on the release of metronidazole from bigel structure. Also, the range of drug release rates was 1.59 - 100% and in 42.85% of studies was >90%. The nature, content, and properties of both organogel and hydrogel and some process variables such as temperature, mixing speed and storage conditions were highlighted as the main influential factors on bigel formation and its bioactivity., Conclusion: Bigels are an innovative structure that provides desired physicochemical and rheological properties for industrial applications. Excellent biocompatibility and in vitro / ex vivo results have been documented for developed bigels. In this regard, an optimal preparation method is very important to show superior therapeutic effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: This systematic review was conducted to evaluate the applicability of the envelope (E) protein in the diagnosis of arboviruses., Methods: This review was performed in accordance with the PRISMA statement. Five databases were explored (PubMed, Web of Science, Scopus, EMBASE, and IEDB). The inclusion and exclusion criteria were applied to study eligibility. After data extraction, the risk of bias and evidence certainty were evaluated according to QUADAS and GRADE assessments, respectively., Results: Eleven studies were included. A total of 11 studies were included in the review. ELISA was the most frequently utilized technique, with two studies employing it for antigen detection and nine for antibodies. The E protein was used as a whole protein, heterologous protein, and peptides. The diagnostic metrics were enhanced by optimizations on techniques, such as antibody capture, competitors, and nanosensors. Monoclonal antibodies showed improved specificity, including in coinfected samples. Seven studies demonstrated a minimal risk of bias, and the evidence certainty was considered moderate for dengue diagnosis., Conclusions: The E protein was successfully employed in different immunological assays with large-scale strategies, enhancing the applicability potential for differential arboviruses' diagnosis. Furthermore, both the antigen design and the implementation of innovative methodologies will have a substantial impact on the quality of the new tests. The PROSPERO protocol related to this work: CRD42021265243., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction/objective: Periodontal disease is a highly prevalent oral pathology in the human population, which has a significant local and systemic impact. Currently, multi-omics analyses, including lipidomics, are fundamental to obtaining an in-depth molecular understanding of the individual. Lipidomics is dedicated to the study of lipid species and their interactions in various health contexts. This specific multi-omics analysis is important for understanding the alteration of metabolism and signaling in disease, identifying biochemical markers, and potential therapeutic targets. This study aimed to carry out a systematic review of the existing scientific literature on lipidomics in periodontal disease and thus determine which molecules have already been analyzed and their potential in this specific disease., Methods: This study followed the recommendations of the PRISMA 2020 methodology. The inclusion criteria used were articles published in indexed journals between 2000 and 2023, written in English, and establishing an exclusive relationship about lipidomics in human periodontal disease. The articles were searched in three different databases., Results: Considering the criteria defined, only six articles were selected and zed individually in detail. In four of the six studies, differences in the lipidome of individuals with periodontal disease were identified. Furthermore, phosphoethanolamine ceramide was found to have potential as a diagnostic biomarker. Finally, the therapeutic potential of a lipoxin A4 analogue was also identified., Conclusion: These results reinforce the need for future research in this area so that the consequences of this disease on the lipidome can be identified., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Clostridium difficile is an opportunistic infection that can lead to antibi-otic-associated diarrhea and toxic megacolon., Objective: This systematic review study aimed to investigate polyphenols' antibacterial and anti-toxin properties and their effects on reducing complications related to C. difficile Infections (CDI)., Methods: This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions., Results: Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Fac-tor-α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) lev-els, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of C. difficile more difficult and prevent it from producing toxins. Furthermore, polyphenols can ex-hibit prebiotic properties, promoting the growth of beneficial Bifidobacterium and Lactobacillus species and consequently regulating gut microbiota, exerting antimicrobial activities against C. dif-ficile. They also induce their beneficial effects by inhibiting the production of C. difficile TcdA and TcdB., Conclusion: Polyphenols have been reported to inhibit C. difficile growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In dental extractions, particularly when local anesthesia is used, it usually offers analgesic relief for a few hours. However, pain can become a notable concern in the immediate postoperative period due to the trauma experienced by both soft and hard oral tissues., Objectives: This systematic review aimed to evaluate the most effective strategies for managing postoperative pain in primary tooth extractions., Methods: Two examiners conducted a search across five electronic databases: MEDLINE (via PubMed), Embase, Scopus, Web of Science, CENTRAL, and OpenGray. Studies were included if they met the following criteria after reviewing their titles and abstracts: they involved children and evaluated pain management following primary tooth extraction. Subsequently, articles that described extractions performed under any form of sedation, were not conducted under local anesthesia, in an outpatient setting, and in children aged 0 to 12 years, or were not randomized controlled trials, were excluded., Results: The search yielded 374 relevant articles, of which 9 were included. Among these, 5 utilized preoperative medications as a pain management strategy, one evaluated low-level laser therapy (LLLT) postoperatively, one assessed calendula drops postoperatively, and another explored virtual reality during the procedure and arnica in solution both pre and postoperatively., Conclusion: Among all the strategies evaluated, the strategy involving analgesics administered 30 minutes before tooth extractions was supported by better-designed studies. However, there is a high risk of bias., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Evodiamine (EVO) is an alkaloid extracted from the dried and nearly ripe fruits of Euodia rutaecarpa and used as an anti-cancer, anti-inflammatory and anti-obesity agent. However, robust evidence of preclinical experiments has been lacking so far. Therefore, the purpose of this article was to investigate the effect of EVO in combination with other treatments on tumors in animal experiments., Methods: A systematic review and meta-analysis were conducted to assess the anti-tumor effect of evodiamine-combined therapy. The search engine and electronic databases included PubMed, Scopus, China Knowledge Resource Integrated Database (CNKI), and SinoMed. The research method was based on the PRISMA checklist., Results: A total of 7 studies and 108 animals were included. As a result, EVO combined therapy was found to be more effective than EVO monotherapy. The SMD was -25.64(95% CI: -5.77 -3.13) in tumor growth. In tumor weight, the SMD was -8.91(95% CI: -16.37, -1.44)., Conclusion: EVO has the potential to alleviate the toxicity of chemotherapeutic agents, which increases the translatability to the clinical situation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Diabetes is one of the important and growing diseases in the world. Among the most common diabetic complications are renal adverse effects. The use of apigenin may prevent the development and progression of diabetes-related injuries. The current study aims to review the effects of apigenin in the treatment of diabetic nephropathy., Methods: In this review, a systematic search was performed based on PRISMA guidelines for obtaining all relevant studies on "the effects of apigenin against diabetic nephropathy" in various electronic databases up to September 2022. Ninety-one articles were obtained and screened in accordance with the predefined inclusion and exclusion criteria. Seven eligible articles were finally included in this review., Results: The experimental findings revealed that hyperglycemia led to the decreased cell viability of kidney cells and body weight loss and an increased kidney weight of rats; however, apigenin administration had a reverse effect on these evaluated parameters. It was also found that hyperglycemia could induce alterations in the biochemical and renal function-related parameters as well as histopathological injuries in kidney cells or tissue; in contrast, the apigenin administration could ameliorate the hyperglycemia-induced renal adverse effects., Conclusion: The results indicated that the use of apigenin could mitigate diabetes-induced renal adverse effects, mainly through its antioxidant, anti-apoptotic, and anti-inflammatory activities. Since the findings of this study are based on experimental studies, suggesting the use of apigenin (as a nephroprotective agent) against diabetic nephropathy requires further clinical studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Liposomal Doxorubicin (Doxil ® ) was one of the first nanoformulations approved for the treatment of solid tumors. Although there is already extensive experience in its use for different tumors, there is currently no grouped evidence of its therapeutic benefits in non-small cell lung cancer (NSCLC). A systematic review of the literature was performed on the therapeutic effectiveness and benefits of Liposomal Doxil ® in NSCLC., Methods: A total of 1022 articles were identified in publications up to 2020 (MEDLINE, Cochrane, Web of Science Core Collection and Scopus). After applying inclusion criteria, the number was restricted to 114, of which 48 assays, including in vitro (n=20) and in vivo (animals, n=35 and humans, n=6) studies, were selected., Results: The maximum inhibitory concentration (IC 50 ), tumor growth inhibition rate, response and survival rates were the main indices for evaluating the efficacy and effectiveness of Liposomal DOX. These have shown clear benefits both in vitro and in vivo , improving the IC 50 of free DOX or untargeted liposomes, depending on their size, administration, or targeting., Conclusion: Doxil ® significantly reduced cellular proliferation in vitro and improved survival in vivo in both experimental animals and NSCLC patients, demonstrating optimal safety and pharmacokinetic behavior indices. Although our systematic review supports its benefits for the treatment of NSCLC, additional clinical trials with larger sample sizes are necessary to obtain more precise clinical data on its activity and effects in humans., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: A substantial number of research studies on metronidazole-related cutaneous symptoms have recently been published. Our objective was to identify and evaluate descriptive studies that described metronidazole-related skin manifestations, therapeutic interventions, and consequences., Methods: A comprehensive literature search was carried out in the PubMed, Scopus, and grey literature databases from inception to April 2022 without any constraints, as well as a snowball search in Google and a search in Google Scholar. Descriptive articles describing metronidazole-related cutaneous manifestations were considered for the review. Two distinct reviewers carried out the research selection, data extraction, and quality assessment; any discrepancies were resolved by consensus with the third reviewer., Results: About 24 out of 4648 descriptive studies, including 26 patients (20 Female patients and 6 male patients), were included in this review. The included studies comprised a range of ages from 16 to 78 years old. Metronidazole was indicated for the treatment of bacterial vaginosis, trichomoniasis, sepsis, anti-infection therapy, perforated appendicitis, rosacea, vaginal discharge, dysentery, acne rosacea, trichomonal vaginitis, lichen planus, liver abscess, facial rosacea, intestinal amoebiasis, and gingivitis. Fixed drug eruption was the most common skin manifestation which was reported in 7 cases included in this review. Cutaneous manifestations were ameliorated by cessation of the offending drug and by apportioning antihistamines, topical steroids, parenteral corticosteroids, emollients, and topical moisturizers., Conclusion: Clinicians and healthcare professionals should be cognizant of the potential cutaneous adverse drug reactions (CADRs) induced by metronidazole to mitigate fatal circumstances. The management of the CADRs appears to respond effectively with immediate drug discontinuation and supportive therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Several studies have shown that the intake of N. sativa has a beneficial effect on metabolic syndrome and related disorders. In this meta-analysis, our primary objective was to assess the impact of Nigella sativa consumption on inflammation and oxidative stress biomarkers among individuals diagnosed with metabolic syndrome and its associated conditions., Methods: Our search was conducted on prominent online databases such as Web of Science, Scopus, PubMed, and EMBASE, utilizing relevant keywords until August 2023., Results: This meta-analysis was performed on 16 RCTs comprising 1033 participants. Our results showed that intake of Nigella sativa significantly decreased CRP (SMD: -0.60; (95% CI: from -0.96 to -0.23); P = 0.00), TNF-α (SMD: -0.53; (95% CI: from -0.74 to -0.53); P = 0.00); IL-6 (SMD: -0.54 ; (95% CI: from -1.01 to -0.07); P = 0.02), and MDA: (SMD: -1.28; (95% CI: from -2.11 to -0.46); P = 0.00) levels. In addition, SOD: (SMD: 1.35; (95% CI, from 0.77 to 1.93); P = 0.00) and TAC (SMD: 2.82; (95% CI, from 0.55 to 5.084); P = 0.01) levels significantly increased in the intervention group compared to the placebo group., Conclusion: Our results showed that THE consumption of N. sativa could be associated with improved oxidative stress and inflammation in patients with metabolic syndrome and related disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: This research aimed to examine the relationship between the intake of statins and the risk of post-stroke pneumonia in a systematic review and meta-analysis study., Methods: An extensive search of published articles on March 2 1st , 2023, was done in several databases, like Web of Science (ISI), PubMed, Cochrane Library, Embase, Scopus, and Google Scholar. The Newcastle Ottawa Scale (NOS) checklist was employed to evaluate the quality of observational studies. Statistical tests (Chi-square test and I 2 ) and graphical techniques (Forest plot) were used to determine whether heterogeneity existed in the meta-analysis studies. Funnel plots and Begg and Egger's tests were used to assess the publication bias., Results: Seven studies (5 cohort and 2 case-control studies) were retrieved to examine the association between statins and post-stroke pneumonia. The sample size of the studies compiled in the meta- analysis was obtained to be 68,966 participants. Meta-analysis demonstrated that the overall odds of post-stroke pneumonia in the statin group was equal to 0.87 (95% CI: 0.67 - 1.13; p-value 0.458). Subgroup analysis indicated that the odds of post-stroke pneumonia in the statin group was equal to 0.93 (95% CI: 0.73-1.18; p-value = 0.558) in the cohort studies, and equal to 0.92 (95% CI: 0.37-2.26; p-value = 0.857) in the case-control studies. The examination of the association between the intake of statins and post-stroke pneumonia showed no evidence of publication bias (Begg's test, p-value = 0.368; Eggers test, p-value = 0.282)., Conclusion: In this study, no relationship has been observed between receiving statins and the risk of post-stroke pneumonia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment and tumor resistance to ionizing radiation are the chief challenges of radiotherapy that can lead to different adverse effects. It was shown that the combined treatment of radiotherapy and natural bioactive compounds (such as silymarin/silibinin) can alleviate the ionizing radiation-induced adverse side effects and induce synergies between these therapeutic modalities. In the present review, the potential radiosensitization effects of silymarin/silibinin during cancer radiation exposure/radiotherapy were studied., Methods: According to the PRISMA guideline, a systematic search was performed for the identification of relevant studies in different electronic databases of Google Scholar, PubMed, Web of Science, and Scopus up to October 2022. We screened 843 articles in accordance with a predefined set of inclusion and exclusion criteria. Seven studies were finally included in this systematic review., Results: Compared to the control group, the cell survival/proliferation of cancer cells treated with ionizing radiation was considerably less, and silymarin/silibinin administration synergistically increased ionizing radiation-induced cytotoxicity. Furthermore, there was a decrease in the tumor volume, weight, and growth of ionizing radiation-treated mice as compared to the untreated groups, and these diminutions were predominant in those treated with radiotherapy plus silymarin/ silibinin. Furthermore, the irradiation led to a set of biochemical and histopathological changes in tumoral cells/tissues, and the ionizing radiation-induced alterations were synergized following silymarin/silibinin administration (in most cases)., Conclusion: In most cases, silymarin/silibinin administration could sensitize the cancer cells to ionizing radiation through an increase of free radical formation, induction of DNA damage, increase of apoptosis, inhibition of angiogenesis and metastasis, etc. However, suggesting the use of silymarin/silibinin during radiotherapeutic treatment of cancer patients requires further clinical studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Stem cell therapy has been considered to play a paramount role in the treatment modalities available for regenerative dentistry. The established beneficial effects of photobiomodulation (PBM) at the cellular level have led to the combined use of these two factors (PBM and stem cells). The main goal of this study was firstly to critically appraise the effects of PBM on periodontal ligament stem cells (PDLSCs), and secondly to explore the most effective PBM protocols applied., Methods: Pubmed, Cochrane, Scopus, Science Direct, and Google Scholar search engines were used to identify experimental in vitro studies in which PBM was applied to cultured PDLSCs. After applying specific keywords, additional filters, and inclusion/exclusion criteria, a preliminary number of 245 articles were narrowed down to 11 in which lasers and LEDs were used within the 630 - 1064 nm wavelength range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines, and a modified Cochrane risk of bias to determine eligibility., Statistical Analysis: The dataset analysed was extracted from the studies with sufficient and clearly presented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables toward study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The significance level for testing was set at α = 0.05., Results: The proliferation rate, osteogenic differentiation, and expression of different indicative genes for osteogenesis and inflammation suppression were found to be positively affected by the application of various types of lasers and LEDs. With regard to the PBM protocol, only the wavelength variable appeared to affect the treatment outcome; indeed, the 940 nm wavelength parameter was found not to exert a favourable effect., Conclusions: Photobiomodulation can enhance the stemness and differentiation capacities of periodontal ligament stem cells. Therefore, for PBM protocols, there remains no consensus amongst the scientific community. Statistical analyses performed here indicated that the employment of a near-infrared (NIR) wavelength of 940 nm may not yield a significant favourable outcome, although those within the 630 - 830 nm range did so. Concerning the fluence, it should not exceed 8 J/cm 2 when therapy is applied by LED devices, and 4 J/cm 2 when applied by lasers, respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Opiorphin has been reported to show a stronger analgesic effect than morphine without causing side effects brought about by morphine-like drugs. Functional opiorphin analogs have been created to enhance its metabolic stability and preserve its potent analgesic effect., Objective: We conducted a systematic review to summarize all opiorphin analogs and identify those with the strongest metabolic stability and antinociceptive effect., Methods: From a total of 122 articles, 11 made it to the quantitative synthesis phase. The included articles were categorized into the type of modifications used to improve the metabolic stability of the peptide, metabolism and toxicity profile, drug absorption and in vitro cytotoxicity, anti-nociceptive effect, the opiorphin analogs' administration in animals or humans, and the type of the test used to test the antinociceptive effect., Results: The substitution of natural amino acid with a non-natural amino acid, side-chain modifications, or D-aminoacid substitution were the most used type of peptide modification to create opiorphin analogs. STR-324 and PEGylated liposomes loaded with opiorphin showed the best metabolism and toxicity performance. [C]-[(CH 2 ) 6 ]-QRF-[S-O-(CH 2 ) 8 ]-R showed high stability in human plasma and stronger inhibitory potency. YQRFSR and PEGylated liposomes loaded with opiorphin showed a stronger antinociceptive effect than the parent opiorphin or morphine, with an analgesic effect of PEGylated liposomes lasting more than 50%. Intravenous administration was the preferred method of opiorphin analog administration, and different tests were used to test the antinociceptive effect., Conclusion: This paper presents the first systematic review discussing opiorphin and opiorphin analogs and identifies the most promising candidates for future research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Individuals with diabetes mellitus (DM) are susceptible to balance, gait and cognitive impairments. Importantly, diabetes affects executive function, a set of cognitive processes critical to everyday cortical function and mobility. Reduced executive function is a risk factor for falls in people with DM. Dual-task testing, the completion of two tasks at once, enables the examination of the cognitive-mobility relationship. A synthesis of the literature on the effects of dual- task testing on the balance and gait of individuals with DM has not been performed., Objective: To systematically review the literature on the effect of dual-task testing on balance and gait in people with DM., Methods: Databases EMBASE, CINAHL, MEDLINE, PsycINFO, Scopus and Web of Science were searched (inception-April 2020)., Inclusion Criteria: participants were adults with a diagnosis of DM, instrumented dual-task balance and/or gait was assessed, and articles were published in English., Results: Ten articles met inclusion criteria- three examined dual-task balance and seven dual-task gait. In people with DM with or without peripheral neuropathy, dual-task resulted in larger sway velocities during standing tests. Individuals with DM and peripheral neuropathy had impaired dual-- task gait; specifically, and more consistently, reduced pace and rhythm compared to controls or people with DM without peripheral neuropathy., Conclusion: The findings support a compromise in the cognitive-mobility relationship of people with DM, and especially in those with peripheral neuropathy. Future research should continue to examine the cognitive-mobility relationship in order to understand the increased prevalence of falls in this population., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurological diseases have different etiological causes. Contemporary, developing an effective treatment for these diseases is an ongoing challenge. Cell therapy is recognized as one of the promising solutions for the treatment of these diseases. Amongst various types of stem cells, bone marrow-derived mesenchymal stem cells (BM-MSC) are known to be the most widely used stem cells. These cells are endowed with appealing properties such as the ability to differentiate into other cell types, including the muscle, liver, glial, and nerve cells. In this review study, we have systematically evaluated the ability of a variety of chemical compounds used in the last ten years to differentiate BM-MSCs into neurons by examining the expression level of beta-tubulin 3 protein. The present study is a systematic search performed at three separate databases, including PubMed, ScienceDirect, and Embase from August 2009 to August 2019. The search results in the three mentioned databases were 323 articles and finally, 8 articles were selected and carefully examined considering the inclusion and exclusion criteria. The results showed that different chemical compounds such as ROCK inhibitors, sex steroid hormones, bFGF, NGF, Noggin, 4 OHT, TSA, VPA, Antidepressants, Neurosteroids (Dex and E2), and DHA are involved in different signaling pathways, such as ERK, AKT, BMP, DHA / GPR40, Rho-dependent phosphorylation, and histone deacetylase inhibitors. Further investigation of these signaling pathways may open the way for better differentiation of BM-MSCs into neurons., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Hepatic steatosis is a frequent condition that afflicts, especially, obese and insulin-resistant patients. Diagnosis is usually made through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested., Objective: This study aimed to determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP- IV) in the treatment of NAFLD., Methods: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE, and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion., Results: 7 studies were used for metanalysis for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 (95% CI 35.23 to 13.57) at 3 months and MD -9.27 (95% CI 10.92 to -7.62) at 6 months of intervention, as well as a reduction of hepatic steatosis via MRI of SMD 0.10 (95% CI 0.31 to 0.50); the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation., Conclusion: Because of the overall poor quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: People living with HIV (PLWHIV) have a 2-fold higher risk of having a cardiovascular event than HIV-negative individuals., Objective: The objective of this article is to estimate the pooled proportion of moderate-high cardiovascular risk in PLWHIV obtained through different scores. In addition, this study also aims to establish the prevalence of dyslipidemia, smoking habits, diabetes and high blood pressure in the included studies., Methods: A bibliographic search was conducted in MEDLINE for studies on cardiovascular risk assessment in PLWHVI that took place during the period of inception to July 2018. The eligibility criteria for inclusion were: cross-sectional or longitudinal studies on HIV-positive adults in which the prevalence of moderate-high cardiovascular risk (or data to calculate it) was reported, and included at least one of the following cardiovascular risk scores: Framingham, ASCVD, D:A:D, Progetto Cuore, PROCAM, SCORE, Regicor, and World Health Organization scores., Results: Bibliographic search identified 278 studies. Finally, thirty-nine peer-reviewed publications were identified for a collective total of 13698 subjects. The pooled prevalence of moderate-high cardiovascular risk in PLWHIV obtained with nine different scores through random-effect modeling was 20.41% (95% CI: 16.77-24.31). The most prevalent concomitant cardiovascular risk factor was dyslipidemia (39.5%), smoking (33.0 %), high blood pressure (19.8%) and diabetes (7.24%)., Conclusion: Data obtained in this systematic review indicate that more than 1 in every five subjects with HIV have a moderate-high cardiovascular risk. In consequence, the burden of cardiovascular disease in PLWHIV represents a public health problem. There is an urgent need to develop strategies to prevent and detect cardiovascular risk effectively in PLWHIV., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: High prevalence of Dental and periodontal problems during the gestation period may have a negative effect on oral health-related quality of life (OHRQoL) in pregnant women. This systematic review aimed to perform a quality assessment and provide a critical overview of the current research available on OHRQoL in pregnant women., Methods: For this systemic review, all original and peer-reviewed human studies, which investigated OHRQoL of women during pregnancy or post- partum period, were searched. Studies were screened in title and abstract for the relevance by two independent investigators. Methodological quality was assessed using modified items recommended by the Newcastle-Ottawa Scale for observational studies., Results: All of the eight included studies had a cross-sectional design. Meta-analysis was not possible due to the heterogeneity of key aspects among the included studies. Thus, the data from the studies were evaluated qualitatively. The overall risk of bias of the included studies was low., Conclusion: The main conclusion of this review is that the presence of signs and symptoms of dental and gingival disease negatively affects the self-perception of OHRQoL in pregnant women. The most affected domains of OHRQoL in pregnant women were related to mental and psychological discomfort, followed by physical and functional problems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The body of evidence on gene-environment interaction (GEI) related to type 2 diabetes (T2D) has grown in the recent years. However, most studies on GEI have sought to explain variation within individuals of European ancestry and results among ethnic minority groups are inconclusive., Objective: To investigate any interaction between a gene and an environmental factor in relation to T2D among ethnic minority groups living in Europe and North America., Methods: We systematically searched Medline and EMBASE databases for the published literature in English up to 25th March 2019. The screening, data extraction and quality assessment were performed by reviewers independently., Results: 1068 studies identified through our search, of which nine cohorts of six studies evaluating several different GEIs were included. The mean follow-up time in the included studies ranged from 5 to 25.7 years. Most studies were relatively small scale and few provided replication data. All studies included in the review included ethnic minorities from North America (Native-Americans, African- Americans, and Aboriginal Canadian), none of the studies in Europe assessed GEI in relation to T2D incident in ethnic minorities. The only significant GEI among ethnic minorities was HNF1A rs137853240 and smoking on T2D incident among Native-Canadians (Pinteraction = 0.006)., Conclusion: There is a need for more studies on GEI among ethnicities, broadening the spectrum of ethnic minority groups being investigated, performing more discovery using genome-wide approaches, larger sample sizes for these studies by collaborating efforts such as the InterConnect approach, and developing a more standardized method of reporting GEI studies are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The pulmonary inflammatory response results from exposure to injurious factors and is associated with oxidative stress, which intensifies the pathological reaction. In this context, limonene, a monoterpene found in citrus fruits, can be a therapeutic alternative for the treatment of this pathology, as it presents known anti-inflammatory and antioxidant actions., Objective: The purpose of this article is to provide an overview of the anti-inflammatory activity of limonene and its capacity to prevent and control respiratory system injuries., Search Strategy: A comprehensive literature search of the Cochrane, Scopus, MEDLINE-PubMed, Web of Science, and Lilacs databases was performed using the keywords: "limonene", "lung", "pulmonary", "airway", "trachea", "lung injury", "respiratory system", "respiratory tract diseases"., Selection Criteria: Studies on the use of limonene in disorders of the respiratory system, published until August 2019, were included. Those that did not use limonene alone or treated lesions in different systems other than the respiratory system, without targeting its anti-inflammatory action were excluded. In addition, review articles, meta-analyses, abstracts, conference papers, editorials/letters and case reports were also excluded., Results: Of the 561 articles found, 64 were in the Cochrane database, 235 in Scopus, 99 in Web of science, 150 in PubMed and 13 in Lilacs. After completing the systematic steps, 25 articles were selected for full reading, after which 7 papers remained in the review. An article was added after a manual literature search, resulting in a total of 8 papers. There was a high level of agreement on inclusion/exclusion among the researchers who examined the papers (Kappa index > 88%)., Conclusion: Limonene has effective anti-inflammatory activity in both preventing and controlling respiratory system injuries., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study is to assess the association between midlife risk factors and dementia., Methods: PubMed and Cochrane library were systematically searched on May 24, 2018, to retrieve prospective cohort studies. The summary Relative Risk (RR) and 95% Confidence Interval (CI) were calculated by the random-effect model to explore the association between midlife risk factors and dementia. Sensitivity analysis and meta-regression were conducted to explore the source of heterogeneity. Publication bias was examined using Begg's and Egger's tests., Results: Thirty-four prospective cohort studies were included, among which 24 were eligible for metaanalysis. A total of 159,594 non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up. The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%, including obesity (RR, 1.78; 95% CI: 1.31-2.41), diabetes mellitus (RR, 1.69; 95% CI: 1.38-2.07), current smoking (RR, 1.61; 95%, CI: 1.32-1.95), hypercholesterolemia (RR, 1.57; 95% CI: 1.19-2.07), and hypertension (borderline blood pressure RR, 1.41; 95% CI: 1.23-1.62 and high Systolic Blood Pressure (SBP) RR, 1.72; 95% CI: 1.25-2.37). However, the sensitivity analyses found that the results of hypercholesterolemia and high SBP were not reliable, which need to be confirmed by more high-quality studies. No influences due to publication bias were revealed. In the systematic review, another three factors (hyperhomocysteinemia, psychological stress, and heavy drinking) were found to be associated with elevated dementia risk. In addition, physical exercise, a healthy diet, and hormone therapy in middle age were associated with the reduction of dementia risk., Conclusions: Middle-aged people with obesity, diabetes, hypertension, or hypercholesterolemia, and current smokers in midlife are at higher risk of developing dementia later in life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Plasma clusterin has been reported to be associated with the pathology, prevalence, severity, and rapid clinical progress of Alzheimer's Disease (AD). However, whether plasma clusterin can be used as a biomarker of AD is inconsistent and even conflicting., Objective: We conducted this study to evaluate the potential of plasma clusterin as the biomarker of AD., Method: PubMed, Embase, and Cochrane databases were systematically searched for studies on the relationship between plasma clusterin levels and AD diagnosis, risk and disease severity. We also compared the difference in Cerebrospinal Fluid (CSF) clusterin levels between AD and control groups. We converted and pooled data using standardized mean difference, Pearson linear regression model and the Cox regression model., Results: A total of 17 articles and 7228 individuals, including 1936 AD were included. The quality ranged from moderate to high. There was no difference in plasma clusterin between AD and control groups (SMD= 0.19 [-0.10, 0.48], p=0.20). Plasma clusterin levels were not correlated with the risk (RR=1.03 [0.97-1.09], p=0.31), the MMSE scores (R=0.33 [-0.06, 0.71], p= 0.09), and the integrated neuropsychological measurements (R=0.21 [-0.20, 0.63], p=0.31) of AD. Additionally, there was no difference in CSF clusterin between AD and control groups (SMD=1.94 [ -0.49, 4.37], p=0.12)., Conclusion: Our meta-analysis suggested no relationship between plasma clusterin levels and the diagnosis, risk, and disease severity of AD and no difference in the CSF clusterin between AD and the control groups. Overall, there is no evidence to support plasma clusterin as a biomarker of AD based on the pooled results., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Osteoarthritis (OA) is a type of progressive rheumatoid disease, which leads to the degeneration of the articular cartilage, synovium, subchondral bone, tendons, and the surrounding ligaments.There are various treatments for knee OA, including pharmaceutical, nonpharmaceutical, and surgical treatments. Considering the chronic nature of the disease as well as the necessity for the long-term use of chemical medications, various side effects could occur that include gastrointestinal bleeding, hypertension, congestive heart failure, hyperkalemia, and kidney failure. Therefore, suitable treatments with fewer side effects should be recommended. Recent investigations suggest increased tendency in people to use Complementary and Alternative Medicine (CAM) for knee OA treatment., Objective: This systematic review aimed to assess the effectiveness and safety of herbal preparations for the treatment of OA., Methods: The searched databases were Cochrane, Scopus, and PubMed. All the selected papers pertained to randomized controlled trials until August 8, 2017 in English in which one or several specific herbs had been used in knee OA treatment., Results: We included 24 randomized trials (involving 2399 women and men). There were several different herbal medicines used within the included trials., Conclusion: The results show that the methods used in these trials may reduce symptoms and the extent of NSAID consumption and enhance the quality of life. Additional trials are suggested to investigate the safety and efficacy of herbs for the treatment of patients with OA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Importance: Alpha1-antitrypsin (AAT) deficiency is a common, but an underdiagnosed genetic condition, affecting 1 in 1500 individuals. It can present insidiously with liver disease in children. Although clinical practice guidelines exist for the management of AAT deficiency, especially with regards to pulmonary involvement, there are no published recommendations that specifically relate to the management of the liver disease and monitoring for lung disease associated with this condition, particularly in children., Objective: To review the literature on the management of AAT deficiency-associated liver disease in adults and children., Evidence Review: A systematic search for articles indexed in PubMed and published was undertaken. Some earlier selected landmark references were included in the review. Search terms included: "alpha1-antitrypsin deficiency"; "liver disease"; "end-stage liver disease"; "liver transplantation" and "preventative management". Recommendations for the management of children with suspected or confirmed AAT deficiency were made according to the Strength of Recommendation Taxonomy scale., Findings: Liver complications arising from AAT deficiency result from the accumulation of mutated AAT protein within hepatocytes. Liver disease occurs in 10% of children, manifested by cholestasis, pruritus, poor feeding, hepatomegaly, and splenomegaly, but the presentation is highly variable. A diagnostic test for AAT deficiency is recommended for these children. Baseline liver function tests should be obtained to assess for liver involvement; however, the only curative treatment for AAT deficiency-associated liver disease is organ transplantation. Conclusion and Relevance: There should be a greater vigilance for AAT deficiency testing among pediatricians. Diagnosis should prompt assessment of liver involvement. Children with AATdeficiency- associated liver disease should be referred to a liver specialist and monitored throughout their lifetimes for the symptoms of AAT-deficiency-related pulmonary involvement., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The effect of endovascular aneurysm repair in patients treated for abdominal aortic aneurysm has not been clearly defined. The objective of the present article was to provide a contemporary literature review and perform an analysis to determine the effect of EVAR on renal function in the early post-operative period and during follow-up., Methods: A systematic review of the literature was undertaken to identify all studies reporting the effect of EVAR on renal function. Outcome data were pooled and combined overall effect sizes were calculated using fixed or random-effects models., Results: Thirty-two studies reporting on 24846 patients were included. Acute renal failure after EVAR occurred with an estimated frequency of 9% (95%CI: 5-16%; I2=97%). Median follow-up period was 19.5 months (range 1-60 months). The estimated frequency of chronic renal failure during follow-up was 7% (95%CI: 3-17%; I2=98%). Hemodialysis was required in 2% (1-3%; I2=97%) of the cases., Conclusion: High-level evidence demonstrating the effect of EVAR on the incidence of acute and chronic renal failure is lacking. Based on the current available data, nearly 10% of patients undergoing EVAR for AAA have an increased risk for renal dysfunction after the procedure. Whether this deterioration may lead to a worse outcome has not been adequately proved., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Polypharmacy remains problematic for individuals ≥65., Objective: To summarise the percentages of patients meeting 2015 STOPP criteria for Potentially Inappropriate Prescriptions (PIPs), 2015 Beers criteria for Potentially Inappropriate Medications (PIMs), and START criteria Potential Prescribing Omissions (PPOs)., Methods: Searches conducted on 2 January 2019 in Medline, Embase, and PubMed identified 562 studies and 62 studies were retained for review. Data were abstracted independently., Results: 62 studies (n=1,854,698) included two RCTs and 60 non-randomised studies. For thirty STOPP/START studies (n=1,245,974) average percentages for ≥1 PIP weighted by study size were 42.8% for 1,242,010 community patients and 51.8% for 3,964 hospitalised patients. For nineteen Beers studies (n = 595,811) the average percentages for ≥1 PIM were 58% for 593,389 community patients and 55.5% for 2,422 hospitalised patients. For thirteen studies (n=12,913) assessing both STOPP/START and Beers criteria the average percentages for ≥1 STOPP PIP were 33.9% and Beers PIMs 46.8% for 8,238 community patients, and for ≥ 1 STOPP PIP were 42.4% and for ≥1 Beers PIM 60.5% for 4,675 hospitalised patients. Only ten studies assessed changes over time and eight found positive changes., Conclusion: PIP/PIM/PPO rates are high in community and hospitalised patients in many countries. RCTs are needed for interventions to: reduce new/existing PIPs/PIMs/PPO prescriptions, reduce prescriptions causing adverse effects, and enable regulatory authorities to monitor and reduce inappropriate prescriptions in real time. Substantial differences between Beers and STOPP/START assessments need to be investigated whether they are due to the criteria, differential medication availability between countries, or data availability to assess the criteria., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cardiac disease is accounted as the leading cause of worldwide morbidity and mortality. The disease is characterized by the overproduction of reactive oxygen and/or nitrogen species (ROS/RNS), and induction of oxidative stress. Cannabidiol (CBD) is a non-psychoactive ingredient of marijuana that has been reported to be safe and well tolerated in patients. Due to its pleiotropic effect, CBD has been shown to exert cytoprotective effects. This study intended to clarify the mechanisms and the potential role of CBD regarding cardiac injuries treatment., Methods: A systematic literature search was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in the electronic databases including PubMed, Web of Science, Scopus, and Embase up to June 2019 using predefined search terms in the titles and abstracts. Accordingly, a set of pre-specified inclusion and exclusion criteria were considered and 8 articles were ultimately included in this study., Results: Our findings demonstrate that CBD has multi-functional protective assets to improve cardiac injuries; preliminary through scavenging of free radicals, and reduction of oxidative stress, apoptosis, and inflammation., Conclusion: CBD can protect against cardiac injuries, mainly through its antioxidative and antiapoptotic effects on the basis of non-clinical studies. The cardioprotective effects of the CBD need to be further studied in welldesigned clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Clinical evaluation of the Endothelial Function (EF) is becoming an essential step in the quality assessment of cardiovascular risk prevention and rational pharmacotherapy of cardiovascular disorders. The existing pieces of evidence suggested that Calcium Channel Blockers (CCB) can induce positive effects on impaired EF., Objective: To evaluate the effects of CCB on EF, we performed a meta-analysis of available data from randomized and placebo-controlled or other treatment-controlled clinical studies encompassing effects of CCB on EF, as measured by Flow-Mediated Dilation (FMD) of the brachial artery., Methods: The relevant clinical studies were searched by systematic exploration of the appropriate databases until November 30, 2017. A random-effect model was conducted. The primary outcome was the percentage change in FMD between the baseline and the final levels in response to investigated drugs., Results: Fifteen randomized clinical studies with 33 arms were identified. CCB improved FMD more pronounced than thiazide diuretics - TD (3 studies, 157 participants, WMD=2.08%, 95% CI=0.35-3.80%; P=0.02). Oppositely, ACE Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) notably improved FMD if compared to CCB (CCB vs. ACEI: 5 studies, 533 participants, WMD = -1.62%, 95% CI = -2.74% to -0.50%; P=0.005; and CCB vs. ARB: 9 studies, 669 participants, WMD = -1.52%, 95% CI = -2.22% to -0.81%; P=0.0001). CCB effects on EF were similar to those evoked by beta blockers or placebo., Conclusion: CCB improved EF to a more prominent extent only if paralleled to TD, while inversely; ACEI and ARB were more effective in augmenting FMD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In recent years, numerous investigations focused on the pleiotropic actions of vitamin D have been carried out. These actions include the participation of this molecule in neurophysiological and neuropathological processes. As a consequence, abundant scientific literature on the role of this vitamin in neurodegenerative entities has emerged, even concerning clinical studies. To identify the level of scientific evidence concerning the relation between vitamin D and neurodegenerative diseases, from a quantitative and qualitative perspective. To describe, by means of a bibliometric analysis, the scientific production and its evolution through time in quantitative terms, regarding the implications of vitamin D in neurodegeneration. To analyse and present the degree of evidence in the aforementioned field of study, a systematic review of the literature focused on the most prevalent neurodegenerative diseases was carried out. We retrieved 848 articles in the bibliometric analysis, the majority of which were dated between the years 2010-2017. The most studied metabolite was the 25(OH)D3 and the most cited disease was multiple sclerosis. In the systematic review, we found studies about Alzheimer's and Parkinson's diseases and again, about multiple sclerosis prominently (in number and quality), with 12 randomised double-blind clinical trials. The research about vitamin D and its relations with neurodegenerative diseases shows a growing evolution over the last decade. More studies are needed to find correlations between the clinical severity of these diseases and the specific status of vitamin D and the genotypes related with them, which seems to be a future trend., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This systematic review evaluated the transplantation of cells derived from adipose tissue for applications in dentistry. SCOPUS, PUBMED and LILACS databases were searched for in vitro studies and pre-clinical animal model studies using the keywords "ADIPOSE", "CELLS", and "PERIODONTAL", with the Boolean operator "AND". A total of 160 titles and abstracts were identified, and 29 publications met the inclusion criteria, 14 in vitro and 15 in vivo studies. In vitro studies demonstrated that adipose- derived cells stimulate neovascularization, have osteogenic and odontogenic potential; besides adhesion, proliferation and differentiation on probable cell carriers. Preclinical studies described improvement of bone and periodontal healing with the association of adipose-derived cells and the carrier materials tested: Platelet Rich Plasma, Fibrin, Collagen and Synthetic polymer. There is evidence from the current in vitro and in vivo data indicating that adipose-derived cells may contribute to bone and periodontal regeneration. The small quantity of studies and the large variation on study designs, from animal models, cell sources and defect morphology, did not favor a meta-analysis. Additional studies need to be conducted to investigate the regeneration variability and the mechanisms of cell participation in the processes. An overview of animal models, cell sources, and scaffolds, as well as new perspectives are provided for future bone and periodontal regeneration study designs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In this Meta-analysis, we aimed to quantify the incidence of complications of different methods of bariatric surgery on diabetic patients., Introduction: Type 2 Diabetes Mellitus (T2DM) is increasing worldwide specifically in obese cases. Additionally, obesity worsens T2DM. Complications of each bariatric surgery method were assessed separately; but, a meta-analysis of these complications and comparison between procedures in T2DM patients have not been investigated previously. The result of this study will help surgeons to choose the most appropriate surgical technique, considering individual conditions for a diabetic patient., Methods: We searched PubMed, Scopus, and ISI for original papers including bariatric surgical procedures for diabetic population and the reported consequences. Data analyses were done using Stata software., Results: Mortality percentage between diabetic and non-diabetic patients was statistically nonsignificant (P = 0.987). Early and late complications were higher in diabetic group in comparison with non-diabetic (6.0% vs. 1.8%, P = 0.024 and 0.6% vs. 0.3%, P = 0.04, respectively). Most prevalent findings in malabsorptive (7.8%, P < 0.001) and restrictive procedures (80%, P < 0.001) were major complications and hypoglycemic episodes, respectively., Conclusion: As our study showed, most of the complications are not necessarily higher in diabetic population but dependent on the method of surgery., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Bipolar Disorder (BD) is a psychiatric disorder characterized by mood disturbances. The pathophysiology of BD is still poorly understood. In the last years, research studies focused on the role of inflammation in BD., Objective: Performed a systematic review and meta-analysis to evaluate the potential effect of the cyclo- oxygenases (Cox)-2 inhibitor Celecoxib adjunct treatment in BD through randomized controlled trials (RCT)., Methods: A search on the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO, Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published from January 1990 to February 2018. A search strategy was developed using the terms: "Bipolar disorder" or "Bipolar mania" or "Bipolar depression" or "Bipolar mixed" or "Bipolar euthymic" and "Celecoxib" or "Cyclooxygenase-2 inhibitors" or "Cox-2 inhibitors" as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. The therapeutic effects of adjunctive treatment with Celecoxib were analyzed. The meta-analysis was performed including the results of the Young Mania Rating Scale (YMRS) at the end of RCT., Results: Three primary studies were included in the systematic review, with a total of 121 patients. The meta-analysis showed a significant effect on the YMRS scores from patients with BD who used Celecoxib adjuvant treatment in comparison to placebo., Conclusion: The systematic review suggests that adjuvant treatment with Celecoxib improves the response of major treatments in patients with BD when compared with adjuvant placebo treatment. Systematic Review Registration Number: The review protocol was registered at PROSPERO (registration number: CRD42017067635); in June 06 2017., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Maintaining the exposure of tacrolimus (Tac) after kidney transplantation (KT) must be necessary to prevent acute rejection (AR) and improve graft survival，but there is still no clear consensus on the optimal Tac target blood concentration and concentration-effect relationship is poorly defined., Methods: We conducted a dose-response meta-analysis to quantitatively assess the association between Tac blood concentration and (AR) or adverse effects after KT. A comprehensive search of PubMed, Embase and Cochrane library databases was conducted to find eligible studies up to 10th September 2018. Unpublished data from patients receiving KT in West China Hospital (Sichuan University, China) were also collected. Both twostage dose-response and one-stage dose-response meta-analysis models were used to improve the statistical power., Results: A total of 4967 individuals from 10 original studies and 1453 individuals from West China Hospital were eligible for the ultimate analysis. In the two-stage dose-response meta-analysis model, we observed a significant non-linear relationship between Tac blood concentration and AR (P < 0.001) with moderate heterogeneity (I2 = 46.0%, P = 0.08). Tac blood concentration at 8ng/ml was associated with the lowest risk of AR (RR: 0.26, 95%CI: 0.13 - 0.54) by reference to 2ng/ml. Tac concentration at 7.0 - 11.0 ng/ml reduced the risk of AR by at least 70%, 5-14 ng/ml by at least 60%, and 4.5 - 14 ng/ml at least 50%. In the one-stage dose-response model, we also found a strong non-linear relationship between Tac and AR (P < 0.001) with moderate heterogeneity (I2 = 41.2%, P = 0.10). Tac concentration of 7.5 ng/ml was associated with the lowest risk of AR (RR: 0.35, 95%CI: 0.16 - 0.77). The blood concentration at 5.5 - 9.5 ng/ml was associated with the reduced AR by at least 60% and 4.5 - 10.5 ng/ml by at least 50% by reference to 2 ng/ml., Conclusion: Maintaining Tac blood concentration at 5 - 9.5 ng/ml within the first year may prevent AR most effectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Fasciolosis, an infectious disorder with a serious public health burden, is caused by two liver flukes belonging to the genus Fasciola. Iran is among the endemic areas for this disease. This study aimed to determine the seroprevalence of human fasciolosis in Iran., Methods: A systematic search was conducted in Embase, PubMed/MEDLINE, Web of Science (WoS), and Google Scholar, as well as Iranian databases including Scientific Information Database (SID), Magiran and Irandoc from January 2000 to June 2016. In order to determine fasciolosis prevalence, the DerSimonian-Laird random model was used. In order to assess the heterogeneity among studies, I2 and Q tests were used. To investigate the source of heterogeneity, meta-regressions based on the year of publication and sample size were performed. Sensitivity analysis was carried out to ensure the stability of obtained results., Results: Eleven relevant studies were included. According to the data analysis a prevalence rate of 2% [95% CI 1-5] was found. No statistically significant relationship between gender and disease prevalence could be detected. We found an OR of developing fasciolosis of 1.67 [95% CI: 0.42 - 6.60] in people who had consumed vegetables versus those who did not eat vegetables, even though this did not yield statistical significance., Conclusion: The findings of the current study can be valuable and help the health-care workers and policy-makers in programming and implementing ad hoc interventions in order to prevent the incidence of disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study was to investigate the prevalence of fascioliasis in humans, cattle, sheep, and goats, done by a systematic review in Iran., Methods: Fifty articles were extracted including Iranian papers such as Google scholar, Magiran, Iran Medex, SID, and Pubmed. Out of these, 21 articles were selected for meta-analysis. Essential information for meta-analysis was extracted from papers and archived in Excel software for calculating by statistical analysis. The variance of each study was obtained using the binomial distribution. Heterogeneity of the studies was surveyed using I2 index. Data were analyzed using a random effect model., Results: Of 21 collected papers, 1,275,506 samples from cow (507,152), sheep (454,882), goat (207,925), and human (105,547) had been surveyed in Iran. Eight studies were conducted on humans and 13 on animals. The prevalence rate obtained in humans was 3% with a confidence interval (CI) of 95% (1%-7%). Prevalence rate obtained in cows, sheep, and goats was 13% with CI of 95% (10%-16%). The highest level of prevalence was reported from cities in the North in animals with a prevalence of 14%. The highest level of prevalence was reported from Gilan in humans with a prevalence of 0.1%., Conclusion: The prevalence of the Fascioliasis in Iran has reduced in recent years, But the importance of the disease has not reduced and there is a possibility of an epidemic. Furthermore, in many cities of Iran, there is no study on the disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Prediction of proteins' secondary structure is one of the major steps in the generation of homology models. These models provide structural information which is used to design suitable ligands for potential medicinal targets. However, selecting a proper tool between multiple Secondary Structure Prediction (SSP) options is challenging. The current study is an insight into currently favored methods and tools, within various contexts., Objective: A systematic review was performed for a comprehensive access to recent (2013-2016) studies which used or recommended protein SSP tools., Methods: Three databases, Web of Science, PubMed and Scopus were systematically searched and 99 out of the 209 studies were finally found eligible to extract data., Results: Four categories of applications for 59 retrieved SSP tools were: (I) prediction of structural features of a given sequence, (II) evaluation of a method, (III) providing input for a new SSP method and (IV) integrating an SSP tool as a component for a program. PSIPRED was found to be the most popular tool in all four categories. JPred and tools utilizing PHD (Profile network from HeiDelberg) method occupied second and third places of popularity in categories I and II. JPred was only found in the two first categories, while PHD was present in three fields., Conclusion: This study provides a comprehensive insight into the recent usage of SSP tools which could be helpful for selecting a proper tool., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purposes: The aims of the present study were to: 1- critically assess the utility of L-3,4- dihydroxy-6-18Ffluoro-phenyl-alanine (18F-DOPA) and O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) Positron Emission Tomography (PET)/Computed Tomography (CT) in patients with high grade glioma (HGG) and 2- describe the results of 18F-DOPA and 18F-FET PET/CT in a case series of patients with recurrent HGG., Methods: We searched for studies using the following databases: PubMed, Web of Science and Scopus. The search terms were: glioma OR brain neoplasm and DOPA OR DOPA PET OR DOPA PET/CT and FET OR FET PET OR FET PET/CT. From a mono-institutional database, we retrospectively analyzed the 18F-DOPA and 18F-FET PET/CT of 29 patients (age: 56 ± 12 years) with suspicious for recurrent HGG. All patients underwent 18F-DOPA or 18F-FET PET/CT for a multidisciplinary decision. The final definition of recurrence was made by magnetic resonance imaging (MRI) and/or multidisciplinary decision, mainly based on the clinical data., Results: Fifty-one articles were found, of which 49 were discarded, therefore 2 studies were finally selected. In both the studies, 18F-DOPA and 18F-FET as exchangeable in clinical practice particularly for HGG patients. From our institutional experience, in 29 patients, we found that sensitivity, specificity and accuracy of 18F-DOPA PET/CT in HGG were 100% (95% confidence interval- 95%CI - 81-100%), 63% (95%CI: 39-82%) and 62% (95%CI: 39-81%), respectively. 18F-FET PET/CT was true positive in 4 and true negative in 4 patients. Sensitivity, specificity and accuracy for 18F-FET PET/CT in HGG were 100%., Conclusion: 18F-DOPA and 18F-FET PET/CT have a similar diagnostic accuracy in patients with recurrent HGG. However, 18F-DOPA PET/CT could be affected by inflammation conditions (false positive) that can alter the final results. Large comparative trials are warranted in order to better understand the utility of 18F-DOPA or 18F-FET PET/CT in patients with HGG., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Antioxidant supplementation has become a common practice among athletes to theoretically achieve a reduction in oxidative stress, promote recovery and improve performance., Objective: To assess the effect of antioxidant supplements on exercise., Methods: A systematic literature search was performed up to January 2019 in MEDLINE via EBSCO and Pubmed, and in Web of Sciences based on the following terms: "antioxidants" [Major] AND "exercise" AND "adaptation"; "antioxidant supplement" AND "(exercise or physical activity)" AND "(adaptation or adjustment)" [MesH]. Thirty-six articles were finally included., Results: Exhaustive exercise induces an antioxidant response in neutrophils through an increase in antioxidant enzymes, and antioxidant low-level supplementation does not block this adaptive cellular response. Supplementation with antioxidants appears to decrease oxidative damage blocking cell-signaling pathways associated with muscle hypertrophy. However, upregulation of endogenous antioxidant enzymes after resistance training is blocked by exogenous antioxidant supplementation. Supplementation with antioxidants does not affect the performance improvement induced by resistance exercise. The effects of antioxidant supplementation on physical performance and redox status may vary depending on baseline levels., Conclusion: The antioxidant response to exercise has two components: At the time of stress and adaptation through genetic modulation processes in front of persistent pro-oxidant situation. Acute administration of antioxidants immediately before or during an exercise session can have beneficial effects, such as a delay in the onset of fatigue and a reduction in the recovery period. Chronic administration of antioxidant supplements may impair exercise adaptations, and is only beneficial in subjects with low basal levels of antioxidants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Type 2 diabetes is a multifactorial disorder influenced by both genetic and environmental factors and is rising dramatically throughout the world. Recently, consideration to dietary acid-base load has been raised as a nutritional indicator that could have metabolic effects., Objective: The aim of this study was to systematically investigate the associations of dietary acid load indices with glucose/insulin homeostasis and type 2 diabetes in a patent based review., Methods: Systematic literature review was conducted using PubMed, Scopus and Google Scholar, from inception up to 10 January 2018. All human studies publications investigated the association of dietary acid load indices (PRAL or NEAP or Pro:K) and incidence of diabetes or glucose/insulin metabolism were included., Results: In all, 174 studies were included for the title and abstract screening. A total of 164 articles were excluded because they did not meet the inclusion criteria. Finally, 10 articles (five crosssectional studies and five cohort studies) in accordance with our inclusion criteria were chosen for further evaluations that were published between 2008 and 2017., Conclusion: Although there are some evidence of an association between dietary acid load and type 2 diabetes, definitive declarations in this regard will be needed to intervention human studies modifying acid-base dietary intake., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Racial/ethnic minorities have among the highest risks for Alzheimer disease and dementia, but remain underrepresented in clinical research studies., Objective: To synthesize the current evidence on strategies to recruit and retain racial/ethnic minorities in Alzheimer disease and dementia clinical research., Methods: We conducted a systematic review by searching CINAHL, EMBASE, MEDLINE, PsycINFO, and Scopus. We included studies that met four criteria: (1) included a racial/ethnic minority group (African American, Latino, Asian, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander); (2) implemented a recruitment or retention strategy for Alzheimer disease or dementia clinical research; (3) conducted within the U.S.; and (4) published in a peer-reviewed journal., Results: Of the 19 included studies, 14 (73.7%) implemented recruitment strategies and 5 (26.3%) implemented both recruitment and retention strategies. Fifteen studies (78.9%) focused on African Americans, two (10.6%) on both African Americans and Latinos, and two (10.5%) on Asians. All the articles were rated weak in the study quality. Four major themes were identified for the recruitment strategies: community outreach (94.7%), advertisement (57.9%), collaboration with health care providers (42.1%), and referral (21.1%). Three major themes were identified for the retention strategies: follow-up communication (15.8%), maintain community relationship (15.8%), and convenience (10.5%)., Conclusion: Our findings highlight several promising recruitment and retention strategies that investigators should prioritize when allocating limited resources, however, additional well-designed studies are needed. By recruiting and retaining more racial/ethnic minorities in Alzheimer disease and dementia research, investigators may better understand the heterogeneity of disease progression among marginalized groups. PROSPERO registration #CRD42018081979., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: People from Latin America (LA) and the Hispanic/Latino community living in the United States (LUS) exhibit a high prevalence of diabetes (DM) and obesity (OB). The Gut Microbiome (GM) is capable of altering energy regulation and glucose metabolism, but for the expression of these diseases a combination of multiple factors such as ethnicity, genetic and nutritional factors are required. A systematic research was conducted to understand if the prevalence of OB and/or DM has an interaction with the GM in LA and LUS., Methods: Research was conducted in PubMed, Web of Science, Scielo, Embase and Google Scholar for articles between 1990 and 2017. It was restricted to human studies published in English, Spanish, or Portuguese that applied genetic techniques to study the GM in LA or LUS and discussed the association with OB and/or DM., Results: Different gut Firmicutes/Bacteroidetes relationships in several populations from LA influenced by geography, diet and lifestyles interacted with OB. Healthy people from the Mexico and US border had the same imbalance between Firmicutes and Bacteroidetes found in OB or Type 2 DM. High levels of Bacteroides and a reduced proportion of Prevotella, Megamonas, and Acidaminococcus were found in newly diagnosed type 1 DM. Once the patient was treated with insulin, an increase of Prevotella levels was seen. Inverse Firmicutes/Bacteroidetes relationship was reported before the development of Type 1 DM., Conclusion: An important relation between GM and OB and/or DM exists in LA and LUS. Further elucidation of pathophysiologic mechanisms is required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Osteoarthritis (OA) is a major global burden creating significant morbidity worldwide. Current curative therapies are expensive, challenging to access and have significant risks, making them infeasible and difficult in many cases. Mesenchymal stem cells (MSCs) can be applied to joints and may regenerate the cartilage damaged in OA, this therapy may be advantageous to existing treatments., Objective: We systematically reviewed clinical trials of MSCs for cartilage repair and provide an overview of the literature in this area here. MEDLINE, Embase, CENTRAL, clinicaltrials.gov and Open- Grey were searched for controlled trials and case series with >5 patents involving MSC therapy for cartilage repair. The controlled trials were meta-analysed and the primary outcome measure was improvement in pain over the control group. A narrative synthesis was composed for the case series., Results: A significant reduction in pain was found with the use of MSCs over controls: Standardised mean difference=-1.27 (95% Confidence intervals -1.95 to -0.58). However, the data was extremely heterogeneous with I2=95%, this may be attributed to differing therapies, clinical indication for treatment and joints treated amongst others. Case series showed improvements in treated patients with a variety of differing treatments and by many outcomes. There were no severe adverse outcomes found across all studies that could be attributed to MSCs, implying their safety., Conclusion: We conclude that MSCs have significant potential for the treatment of OA, however, larger, more consistent trials are needed for conclusive analysis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Mesenchymal stem cells (MSC) are unique in their ability to self-renew and differentiate into one of many lineage possibilities. It is therefore integral to preserve these qualities to prevent the far reaching effects of a defective stem cell. Human mesenchymal stem cells (hMSC) are precursors for and can differentiate into osteoblasts, adipocytes and chondrocytes. They were originally found in the bone marrow, but have also been located in the umbilical cord, adipose tissue and muscle. Few studies have been conducted into the in vivo effects of age on these cells. This contribution reviews current knowledge surrounding the effects of age on the characteriation and differentiation of human mesenchymal stem cells., Method: 471 articles were found using a combination of Online published articles from January 1983 to January 2016 were searched using the Cochrane Library, PubMed, Medline, Scopus, Web of Science and Science Direct databases. There were no existing systematic reviews on this research topic., Results: Nine studies were identified that met the predefined selection criteria. Three studies were used to assess the effects of ageing on characterisation of hMSC with no conclusive results. The cumulative results of these studies show that the effect of ageing on characterisation of hMSC remains inconclusive. Seven studies were used to assess the differentiation potentials of hMSC showing that age either decreased or altered lineage preference in hMSC differentiation., Conclusion: There is indication that ageing affects hMSC characterisation and differentiation, however it is not conclusive. There are not enough high quality controlled clinical trials to make reliable conclusions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated., Objective: The objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity., Methods: A systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics 'PCR' and 'Schizophrenia', by using MESH terms., Results: An immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation., Conclusion: CRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)