Vulnerability of Eastern Tropical Pacific chondrichthyan fish to climate change.

Climate change is an environmental emergency threatening species and ecosystems globally. Oceans have absorbed about 90% of anthropogenic heat and 20%-30% of the carbon emissions, resulting in ocean warming, acidification, deoxygenation, changes in ocean stratification and nutrient availability, and more severe extreme events. Given predictions of further changes, there is a critical need to understand how marine species will be affected. Here, we used an integrated risk assessment framework to evaluate the vulnerability of 132 chondrichthyans in the Eastern Tropical Pacific (ETP) to the impacts of climate change. Taking a precautionary view, we found that almost a quarter (23%) of the ETP chondrichthyan species evaluated were highly vulnerable to climate change, and much of the rest (76%) were moderately vulnerable. Most of the highly vulnerable species are batoids (77%), and a large proportion (90%) are coastal or pelagic species that use coastal habitats as nurseries. Six species of batoids were highly vulnerable in all three components of the assessment (exposure, sensitivity and adaptive capacity). This assessment indicates that coastal species, particularly those relying on inshore nursery areas are the most vulnerable to climate change. Ocean warming, in combination with acidification and potential deoxygenation, will likely have widespread effects on ETP chondrichthyan species, but coastal species may also contend with changes in freshwater inputs, salinity, and sea level rise. This climate-related vulnerability is compounded by other anthropogenic factors, such as overfishing and habitat degradation already occurring in the region. Mitigating the impacts of climate change on ETP chondrichthyans involves a range of approaches that include addressing habitat degradation, sustainability of exploitation, and species-specific actions may be required for species at higher risk. The assessment also highlighted the need to further understand climate change's impacts on key ETP habitats and processes and identified knowledge gaps on ETP chondrichthyan species.

El cambio climático es una emergencia medioambiental que amenaza a especies y ecosistemas en todo el mundo. Los océanos han absorbido alrededor del 90% del calor antropogénico y entre el 20% y el 30% de las emisiones de carbono, lo que ha provocado su calentamiento, acidificación, desoxigenación, cambios en la estratificación de los océanos y en la disponibilidad de nutrientes, así como fenómenos extremos más pronunciados. Dadas las predicciones de cambios, hay una importante necesidad de entender cómo las especies marinas se verán afectadas. En este estudio utilizamos una Evaluación Integrada de Riesgos para evaluar la vulnerabilidad de 132 condrictios del Pacífico Tropical Oriental (PTO) a los impactos del cambio climático. Adoptando un enfoque preventivo, estimamos que la vulnerabilidad general al cambio climático es Alta para casi una cuarta parte (23%) de las especies de condrictios del PTO evaluadas y Moderada para gran parte del resto (76%). La mayoría de las especies altamente vulnerables son batoideos (77%), y una gran proporción de éstas (90%) son especies costeras o especies pelágicas que utilizan los hábitats costeros como áreas de crianza. Seis especies de batoideos tuvieron una vulnerabilidad Alta en los tres componentes de la evaluación. Esta evaluación indica que las especies costeras, en particular las que dependen de áreas de crianza costeras, son las más vulnerables al cambio climático. Es probable que el calentamiento de los océanos, junto con la acidificación y la posible desoxigenación, tenga efectos generalizados sobre las especies de condrictios del PTO, pero las especies costeras se verán también afectadas por los cambios en los aportes de agua dulce, la salinidad y el aumento del nivel del mar. Esta vulnerabilidad relacionada con el clima se ve agravada por otros factores antropogénicos que ya se están produciendo en la región, como la sobrepesca y la degradación del hábitat. La mitigación de los impactos del cambio climático sobre los condrictios del PTO implica medidas que incluyan abordar la degradación del hábitat y la sostenibilidad de la explotación pesquera, y acciones para las especies de mayor riesgo son necesarias. Esta evaluación también destaca la necesidad de comprender mejor los impactos del cambio climático en los hábitats y procesos clave del PTO y las lagunas de conocimiento identificadas en relación con las especies de condrictios del PTO.

A Docking and Network Pharmacology Study on the Molecular Mechanisms of Curcumin in Dental Caries and Streptococcus mutans.

BACKGROUND: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. METHODS: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. RESULTS: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. CONCLUSIONS: Curcumin affects both host carious processes and Streptococcus mutans.

Association between fluoride intake from drinking water and severity of dental fluorosis in Northern and Western Mexico: systematic review and meta-analysis.

BACKGROUND: Dental fluorosis (DF) is caused by excessive exposure to fluoride during odontogenesis and leads to various changes in the development of tooth enamel. Some regions in Mexico are considered endemic fluorosis zones due to the high fluoride content in drinking water. The objective of this study was to perform a systematic review and meta-analysis to identify the association between the concentration of fluoride in drinking water and the severity of dental fluorosis in northern and western Mexico. METHODS: This protocol was registered in the PROSPERO database (ID: CRD42023401519). The search for information was carried out in the PubMed/Medline, Scopus, SpringerLink, and Google Scholar databases between January 2015 and October 2023. The overall relative risk was calculated using the inverse of variance approach with the random effects method. The RoB 2.0 tool was used to construct risk plots. RESULTS: Eleven articles were analyzed qualitatively, and most of the included studies presented at least one level of DF severity; six articles were analyzed quantitatively, dividing them into two regions. In North region it was observed a higher prevalence of severe TF cases, corresponding to ≥ TF 5 category (4.78) [3.55, 6.42]. In the West region, most of the included studies presented a higher prevalence of less severe cases, corresponding to ≤ TF 4, in comparison with the North region (0.01) [0.00, 0.52], interpreted as a protective effect. CONCLUSION: The concentrations of fluorides in drinking water are reportedly high in these regions and are directly related to the severity of dental fluorosis experienced by the inhabitants. In the Northern region exists a major concentration of fluoride in drinking water compared with the Western region as well as a prevalence of higher severity cases of dental fluorosis.

A decade of submersible observations revealed temporal trends in elasmobranchs in a remote island of the Eastern Tropical Pacific Ocean.

No-take marine protected areas (MPAs) can mitigate the effects of overfishing, climate change and habitat degradation, which are leading causes of an unprecedented global biodiversity crisis. However, assessing the effectiveness of MPAs, especially in remote oceanic islands, can be logistically challenging and often restricted to relatively shallow and accessible environments. Here, we used a long-term dataset (2010-2019) collected by the DeepSee submersible of the Undersea Hunter Group that operates in Isla del Coco National Park, Costa Rica, to (1) determine the frequency of occurrence of elasmobranch species at two depth intervals (50-100 m; 300-400 m), and (2) investigate temporal trends in the occurrence of common elasmobranch species between 2010 and 2019, as well as potential drivers of the observed changes. Overall, we observed 17 elasmobranch species, 15 of which were recorded on shallow dives (50-100 m) and 11 on deep dives (300-400 m). We found a decreasing trend in the probability of occurrence of Carcharhinus falciformis over time (2010-2019), while other species (e.g. Taeniurops meyeni, Sphyrna lewini, Carcharhinus galapagensis, Triaenodon obesus, and Galeocerdo cuvier) showed an increasing trend. Our study suggests that some species like S. lewini may be shifting their distributions towards deeper waters in response to ocean warming but may also be sensitive to low oxygen levels at greater depths. These findings highlight the need for regional 3D environmental information and long-term deepwater surveys to understand the extent of shark and ray population declines in the ETP and other regions, as most fishery-independent surveys from data-poor countries have been limited to relatively shallow waters.

Ethnomedicinal Study and Evaluation of the Anxiolytic-like and Diuretic Effects of the Orchid Stanhopea tigrina Bateman ex Lindl-(Orchidaceae).

Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.

Celecoxib Decreases the Need for Rescue Analgesics after Total Knee Arthroplasty: A Meta-Analysis.

This systematic review and meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of celecoxib after total knee arthroplasty. Keywords in the PubMed and Scopus databases were used to find article abstracts. Each included clinical trial was assessed using the Cochrane Collaboration risk of bias tool, and we extracted data on postoperative pain assessment using the Visual Analogue Scale (VAS) at rest, ambulation, and active range of motion, rescue analgesic intake, and adverse effects. Inverse variance tests with mean differences were used to analyze the numerical variables. The Mantel-Haenszel statistical method and the odds ratio were used to evaluate the dichotomous data. According to this qualitative assessment (n = 482), two studies presented conclusions in favor of celecoxib (n = 187), one showed similar results between celecoxib and the placebo (n = 44), and three clinical trials did not draw conclusions as to the effectiveness of celecoxib versus the placebo (n = 251). Moreover, the evaluation of the rescue analgesic intake showed that the patients receiving celecoxib had a lower intake compared to patients receiving a placebo (n = 278, I2 = 82%, p = 0.006, mean difference = -6.89, 95% IC = -11.76 to -2.02). In conclusion, the pooled analysis shows that administration of celecoxib alone results in a decrease in rescue analgesic consumption compared to a placebo after total knee surgery.

Modulation of myeloid-derived suppressor cell functions by oral inflammatory diseases and important oral pathogens.

The oral cavity presents a diverse microbiota in a dynamic balance with the host. Disruption of the microbial community can promote dysregulation of local immune response which could generate oral diseases. Additionally, alterations in host immune system can result in inflammatory disorders. Different microorganisms have been associated with establishment and progression of the oral diseases. Oral cavity pathogens/diseases can modulate components of the inflammatory response. Myeloid-derived suppressor cells (MDSCs) own immunoregulatory functions and have been involved in different inflammatory conditions such as infectious processes, autoimmune diseases, and cancer. The aim of this review is to provide a comprehensive overview of generation, phenotypes, and biological functions of the MDSCs in oral inflammatory diseases. Also, it is addressed the biological aspects of MDSCs in presence of major oral pathogens. MDSCs have been mainly analyzed in periodontal disease and Sjögren's syndrome and could be involved in the outcome of these diseases. Studies including the participation of MDSCs in other important oral diseases are very scarce. Major oral bacterial and fungal pathogens can modulate expansion, subpopulations, recruitment, metabolism, immunosuppressive activity and osteoclastogenic potential of MDSCs. Moreover, MDSC plasticity is exhibited in presence of oral inflammatory diseases/oral pathogens and appears to be relevant in the disease progression and potentially useful in the searching of possible treatments. Further analyses of MDSCs in oral cavity context could allow to understand the contribution of these cells in the fine-tuned balance between host immune system and microorganism of the oral biofilm, as well as their involvement in the development of oral diseases when this balance is altered.

A New Method for Classifying Scenes for Simultaneous Localization and Mapping Using the Boundary Object Function Descriptor on RGB-D Points.

Scene classification in autonomous navigation is a highly complex task due to variations, such as light conditions and dynamic objects, in the inspected scenes; it is also a challenge for small-factor computers to run modern and highly demanding algorithms. In this contribution, we introduce a novel method for classifying scenes in simultaneous localization and mapping (SLAM) using the boundary object function (BOF) descriptor on RGB-D points. Our method aims to reduce complexity with almost no performance cost. All the BOF-based descriptors from each object in a scene are combined to define the scene class. Instead of traditional image classification methods such as ORB or SIFT, we use the BOF descriptor to classify scenes. Through an RGB-D camera, we capture points and adjust them onto layers than are perpendicular to the camera plane. From each plane, we extract the boundaries of objects such as furniture, ceilings, walls, or doors. The extracted features compose a bag of visual words classified by a support vector machine. The proposed method achieves almost the same accuracy in scene classification as a SIFT-based algorithm and is 2.38× faster. The experimental results demonstrate the effectiveness of the proposed method in terms of accuracy and robustness for the 7-Scenes and SUNRGBD datasets.

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Dactylopius opuntiae [Cockerell] Could Be a Source of Antioxidants for the Preservation of Beef Patties.

Dactylopius opuntiae is an insect pest that contains at least carminic acid, which has antioxidant properties. Since there is a relationship between the antioxidant ability and preservative action of compounds applied to meat products, the purpose of this study was to evaluate the antioxidant activity and usefulness of a D. opuntiae extract for beef patty preservation. The insects were bred and processed to obtain a liquid extract. For the extract, its carminic acid content, antioxidant activity against two free radicals, and actions on food quality parameters were determined. The D. opuntiae dry powder contained 2.91% w/w carminic acid, while the liquid extract exhibited an IC50 value of 3437.8 ± 67.8 and 19633.0 ± 674.5 µg/mL against the DPPH and ABTS radicals. Nevertheless, these antioxidant actions were lower than those found in a D. coccus extract. The D. opuntiae extract improved in a short time the redness and yellowness, eliminated the unfavorable effect of their vehicle on the MetMb level, and greatly reduced the TBARS formation. For the first time, an extract of D. opuntiae was applied to beef patties, and its beneficial antioxidant action on meat acceptance parameters was confirmed, which has potential commercial applications.

Analgesic Efficacy and Safety of Tapentadol Immediate Release in Bunionectomy: A Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the analgesic effect of different doses of tapentadol immediate release (IR) and its adverse effects after a bunionectomy. Pubmed, Cochrane, Lilacs, Medline, and Imbiomed were used to identify abstracts of scientific publications related to the keywords of this systematic review (PROSPERO ID CRD42023437295). Moreover, the risk of bias in all included articles was assessed using the Cochrane Collaboration risk of bias tool. Data on the sum of pain intensity, total pain relief, global assessment, and adverse effects were extracted. The statistical method of inverse variance with means difference was used to evaluate the numerical data and the Mantel-Haenszel and Odd Ratio test to analyze the dichotomous data. In addition, the number needed to treat, the number needed to harm, and the 95% confidence intervals were calculated. A qualitative evaluation (n = 2381) was carried out according to the conclusions of the authors. Tapentadol (n = 1772) was more effective in relieving postoperative pain than the placebo (n = 609) after a bunionectomy. In addition, the analgesic efficacy of IR tapentadol (n = 1323) versus the placebo (n = 390) was evaluated in a total of 1713 patients using a global evaluation of the treatments. All three doses of IR tapentadol showed better results compared to the placebo after a bunionectomy. Finally, the adverse effects have a direct relationship with the dose, and the greatest number of adverse effects are most observed with tapentadol IR 100 mg (n = 2381). It is concluded that tapentadol IR (100 mg) leads to the best satisfaction score in this meta-analysis.

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes.

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein-protein and target-compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa's antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED50) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.

Molecular mechanism of curcumin on periodontitis: A pharmacological network study.

OBJECTIVE: This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy. METHODS: The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein-protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin. RESULTS: Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin. CONCLUSION: The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin.

Artificial Intelligence for Image Analysis in Oral Squamous Cell Carcinoma: A Review.

Head and neck tumor differential diagnosis and prognosis have always been a challenge for oral pathologists due to their similarities and complexity. Artificial intelligence novel applications can function as an auxiliary tool for the objective interpretation of histomorphological digital slides. In this review, we present digital histopathological image analysis applications in oral squamous cell carcinoma. A literature search was performed in PubMed MEDLINE with the following keywords: "artificial intelligence" OR "deep learning" OR "machine learning" AND "oral squamous cell carcinoma". Artificial intelligence has proven to be a helpful tool in histopathological image analysis of tumors and other lesions, even though it is necessary to continue researching in this area, mainly for clinical validation.

Widespread diversity deficits of coral reef sharks and rays.

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities.

Isobolographic analysis of the ciprofloxacin-gentamicin combination against beta-lactamase-producing Staphylococcus aureus.

BACKGROUND: Bacterial multi-resistance is a serious global problem that continues to worsen over time due to multiple factors. Among these factors, it is important to highlight the clinical misuse of antibiotics and the mechanisms that microorganisms have developed to protect themselves from these drugs. In this sense, Staphylococcus aureus (S. aureus) is a pathogen that has found a way to resist many of the drugs currently in use, so infections by this bacterium represent a serious clinical problem. OBJECTIVES: The purpose of this study was to determine the type of interaction between ciprofloxacin and gentamicin against beta-lactamase-producing S. aureus using isobolographic analysis. METHODS: Ciprofloxacin (0.5-0.05 mg/mL) and gentamicin (10-1 mg/mL) were used to make concentration-dependent curves for each individual drug. Thereafter, the 50 inhibitory concentration (IC50 ) of each drug was obtained, and different proportions of the ciprofloxacin-gentamicin combination-0.5:0.5, 0.8:0.2, 0.2:0.8, 0.9:0.1, 0.1:0.9, 0.95:0.05, and 0.05:0.95-were evaluated. The isobolographic analysis and the interaction index were used to analyze the data. RESULTS: The isobolographic evaluation of the combination showed that the ratios 0.5:0.5, 0.8:0.2, 0.2:0.8, and 0.9:0.1 produced a synergistic anti-staphylococcal effect, and the 0.95:0.05 ratio induced an additive antibacterial effect. Finally, the 0.1:0.9 and 0.05:0.95 ratios of the combination presented antagonistic effects against S. aureus. On the other hand, the interaction index showed similar results to the isobolographic analysis. CONCLUSION: The isobolographic results of this in vitro assay show that the ciprofloxacin-gentamicin combination induces synergistic, additive, and antagonistic antimicrobial effects against S. aureus.

In Vivo Neuropharmacological Effects of Neophytadiene.

Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera, plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.

Analgesic Efficacy of COX-2 Inhibitors in Periodontal Surgery: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to evaluate the analgesic efficacy of COX-2 inhibitors versus other drugs in periodontal surgery. Two researchers searched PubMed, Google Scholar, ACM Digital, BASE, EBSCOhost, Scopus, or Web of Science for clinical trials using various combinations of words. All articles that met the selection criteria were assessed using the Cochrane Collaboration's risk of bias tool. For data analysis, the inverse variance and mean difference statistical method was used with Review Manager 5.3 software for Windows. According to the conclusion of each study (qualitative evaluation), only one clinical trial had results in favor of a COX-2 inhibitor when compared to placebo, one clinical study informed that a COX-2 was better that an active control, four studies showed similar analgesic efficacy to active controls, and one clinical study informed the analgesic effect of one celecoxib-caffeine combination in comparison with celecoxib alone and placebo (n = 337). The COX-2 inhibitors showed a decrease in the rescue analgesic consumption (n = 138; I2 = 15%; mean difference = -0.31; 95%CIs = -0.6 to -0.01), and lower pain intensity at four hours (n = 178; I2 = 0%; mean difference = -2.25; 95%CIs = -2.94 to -1.55; p = 0.00001) when compared to active controls after periodontal surgery. In conclusion, the data indicate that COX-2 agents produce better pain relief in comparison to placebo and other drugs after periodontal surgery.

Emerging avenues linking myeloid-derived suppressor cells to periodontal disease.

Periodontal disease is one of the most common inflammatory disorders in humans. Gingivitis is the mildest form of periodontal disease and its progression can lead to periodontitis, an inflammatory disease characterized by soft tissue damage that can lead to progressive destruction of the periodontal ligament and alveolar bone. Diverse populations of immune cells are involved in periodontal disease. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous group of immature myeloid cells derived from hematopoietic precursor cells and exhibit T cell immunosuppressive functions that are thought to be involved in periodontal disease. Therefore, MDSCs have been recently analyzed in the context of this disease. In this review, we discuss the most recent advances in the characterization of the biological aspects, subpopulations, and traffic of MDSCs, as well as their immunosuppressive and osteoclastogenic activity in the context of periodontal disease and in the presence of key periodontal pathogens.