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Interlayer excitons (IXs) in van der Waals heterostructures with static out of plane dipole moment and long lifetime show promise in the development of exciton based optoelectronic devices and the exploration of many body physics. However, these IXs are not always observed, as the emission is very sensitive to lattice mismatch and twist angle between the constituent materials. Moreover, their emission intensity is very weak compared to that of corresponding intralayer excitons at room temperature. Here we report the room-temperature realization of twist angle independent momentum direct IX in the heterostructures of bulk PbI2 and bilayer WS2. Momentum conserving transitions combined with the large band offsets between the constituent materials enable intense IX emission at room temperature. A long lifetime (â¼100 ns), noticeable Stark shift, and tunability of IX emission from 1.70 to 1.45 eV by varying the number of WS2 layers make these heterostructures promising to develop room temperature exciton based optoelectronic devices.
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Memristors-based integrated circuits for emerging bio-inspired computing paradigms require an integrated approach utilizing both volatile and nonvolatile memristive devices. Here, an innovative architecture comprising of 1D CVD-grown core-shell heterostructures (CSHSs) of MoO2-MoS2 is employed as memristors manifesting both volatile switching (with high selectivity of 107 and steep slope of 0.6 mV decade-1) and nonvolatile switching phenomena (with Ion/Ioff ≈103 and switching speed of 60 ns). In these CSHSs, the metallic core MoO2 with high current carrying capacity provides a conformal and immaculate interface with semiconducting MoS2 shells and therefore it acts as a bottom electrode for the memristors. The power consumption in volatile devices is as low as 50 pW per set transition and 0.1 fW in standby mode. Voltage-driven current spikes are observed for volatile devices while with nonvolatile memristors, key features of a biological synapse such as short/long-term plasticity and paired pulse facilitation are emulated suggesting their potential for the development of neuromorphic circuits. These CSHSs offer an unprecedented solution for the interfacial issues between metallic electrodes and the layered materials-based switching element with the prospects of developing smaller footprint memristive devices for future integrated circuits.
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Metal nanoparticles (NPs) can be employed to modify the emission level of a dye emitter by tailoring the spectral overlap of the optical gain and localized surface plasmon resonance (LSPR). In the case of plasmonic random lasers, tuning the spectral overlap by manipulating metal NPs changes the scattering properties of the system, which is crucial in random lasers (RLs). In order to overcome this drawback, the emitter gain spectrum across the LSPR is tuned by appropriately choosing various dye emitters. A system with Au nanoislands (NIs) randomly distributed on the surface of vertically aligned ZnO nanorods on a glass substrate coated with three different dye emitters has been employed to study the metal-gain interaction as a function of spectral overlap. It is observed that the photoluminescence is quenched in the presence of Au NIs for all the three dye emitters; however, the degree of quenching is found to be directly proportional to the extent of spectral overlap of the LSPR and the fluorophore emission spectrum, with the resonantly coupled systems exhibiting higher random lasing thresholds. However, a dequenching of the emission is observed under spectrally off-resonant conditions, leading to a lower threshold RL. The effect of tailoring of the metal-gain interaction on the coherent and incoherent intensity components of RL emission is studied to elucidate the contrasting results of photoluminescence and RL emission. As the optical gain shifts away from the LSPR peak, the RL emission is dominated by the coherent intensity. The speckle-like field distributions of the RL modes couple to the plasmonic nanocavities along with a reduced absorption loss for the off-resonant case, leading to an enhanced stimulated emission. Hence, a synergy between random laser modes, plasmonic nanocavities and optimum spectral overlap has been utilized as a tool to dequench the plasmon quenched fluorophore emission.
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OBJECTIVE: This systematic review and meta-analysis aimed to estimate the global prevalence of gingival recession (GR) in the general population. MATERIALS AND METHODS: Population-based observational studies reporting the prevalence of GR and published from 1991 to 2021 were identified from five electronic databases and manual searches. Risk of bias was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence Studies. The pooled prevalence of GR was calculated by using a random-effect model. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to summarize the overall certainty of evidence. RESULTS: A total of 15 studies involving 37,460 participants were included. The overall pooled prevalence was 78.16% at the minimal reported threshold values and 84.92% at ≥1 mm "cut-off" with high heterogeneity among studies. A separate analysis for the buccal GR revealed a pooled prevalence of 75.42%. The risk of bias was found to be high for 10 and low for 5 studies. The overall certainty of the evidence was assessed to be very low. CONCLUSION: More than two-thirds of the population worldwide was found to be affected by GR. Studies with standard case definition and less heterogeneity are required to accurately estimate the prevalence of GR.
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Recesión Gingival , Humanos , Recesión Gingival/epidemiología , Prevalencia , Estudios TransversalesRESUMEN
Soil and water pollution, rapid industrialization, contaminated irrigation-water, increased waste-production and surge in agricultural land leads to the accumulation of Heavy Metals (HM) with time. HM contamination has raised concern over the past years and new remediation strategies are required to deal with it. HM-contaminated soil is often used for the production of food, which makes a gateway for toxic metals into the food-chain, thereby affecting food security and human health. To avoid HM-toxicity, decontamination of important resources is essential. Therefore, exploring phytoremediation for the removal, decomposition and detoxification of hazardous metals from HM-contaminated sites is of great significance. Hyper-accumulator plants can efficiently remove HMs. However, despite many hyper-accumulator plant species, there is a research gap in the studies of phytotechnology. Hence biotechnological efforts advocating omics studies i.e. genomics, transcriptomics, proteomics, metabolomics and phenomics are in order, the purpose being to select and enhance a plant's potential for the process of phytoremediation to be more effective. There is a need to study newly developed high-efficiency hyper-accumulator plants as HM-decontaminator candidates for phytoremediation and phytomining. Therefore, this review focuses on various strategies and bio-technological methods for the removal of HM contaminants from sites, with emphasis on the advancement of phytoremediation, along with applications in cleaning up various toxic pollutants.
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Metales Pesados , Contaminantes del Suelo , Humanos , Biodegradación Ambiental , Contaminantes del Suelo/análisis , Plantas , Metales Pesados/análisis , SueloRESUMEN
OBJECTIVES: Mucosal fenestrations are infrequent and often challenging to treat depending on the extent of soft and hard tissue destruction. This article presents the successful management of a relatively larger mucosal fenestration associated with complete absence of buccal bone plate in a mandibular incisor secondary to trauma-induced periapical pathosis. CLINICAL CONSIDERATIONS: After non-surgical endodontic therapy, surgery was performed for debridement of the osseous defect, root resection/shaping, connective tissue graft (CTG) placement on the affected root surface and platelet rich fibrin (PRF) in periapical osseous defect rather than use of bone graft and/or barrier membrane. Healing was uneventful, however, a small mucosal defect remained at 2 weeks follow-up. After 3 months of primary surgery, a corrective surgery was performed utilizing an "incision-free" approach i.e. tunnel technique with CTG in contrast to the contemporary flap approach. At 18 months follow-up, complete closure of the mucosal defect with a thick gingival biotype, normal sulcus depth, and good esthetic outcome were achieved. No recurrence and any clinical signs of infection or inflammation were observed. CONCLUSIONS: Based on the outcomes of present case, an early intervention utilizing the minimally invasive surgical therapy and autologous biomaterials may be considered a viable approach to treat such complex lesions. CLINICAL SIGNIFICANCE: Endodontic therapy in combination with PRF and CTG appears to provide successful outcomes in treatment of a large mucosal fenestration with periapical osseous defect.
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Fibrina Rica en Plaquetas , Tejido Conectivo/trasplante , Estudios de Seguimiento , Encía , Incisivo/patologíaRESUMEN
OBJECTIVE: In the current scenario of medical sciences, homeopathy, the most popular system of therapy, is recognized as one of the components of complementary and alternative medicine (CAM) across the world. Despite, a long debate is continuing whether homeopathy is just a placebo or more than it, homeopathy has been considered to be safe and cost-effectiveness therapeutic modality. A number of human ailments ranging from common to serious have been treated with homeopathy. However, selection of appropriate medicines against a disease is cumbersome task as total spectrum of symptoms of a patient guides this process. Available data suggest that homeopathy has potency not only to treat various types of cancers but also to reduce the side effects caused by standard therapeutic modalities like chemotherapy, radiotherapy or surgery. Although homeopathy has been widely used for management of cancers, its efficacy is still under question. In the present review, the anti-cancer effect of various homeopathic drugs against different kinds of cancers has been discussed and future course of action has also been suggested.
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Homeopatía , Neoplasias , Humanos , Neoplasias/terapiaRESUMEN
Hemoglobins (Hbs) are evolutionarily conserved small globular proteins with characteristic 3-over-3 α-helical sandwich structure that is typically known as "globin fold". Hbs have been found to be involved in diverse biological functions and the characteristic property of oxygen transportation is relatively a recent adaptation. Drosophila genome possesses three globin genes (glob1, glob2, and glob3) and it was previously reported that adequate expression of glob1 is required for various aspects of development, and also to regulate the cellular level of reactive oxygen species (ROS). The present study illustrates the explicit role of glob1 gene in Drosophila development. We demonstrate a dynamic expression pattern of glob1 in larval tissues which largely concentrate around F-actin rich structures and also co-precipitate. Reduced expression of glob1 leads to developmental abnormalities which appeared to be largely mediated by inappropriately formed F-actin based cytoskeletal structures. Our subsequent analysis in FLP/FRT mediated somatic clones establishes specific role of Drosophila glob1 in maintenance of the integrity of F-actin based cytoskeleton during development. For the first time, we report interaction between Glob1 and actin, and propose a novel role of glob1 in maintenance of F-actin based cytoskeleton in Drosophila.
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Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica/fisiología , Globinas/metabolismo , Animales , Proteínas de Drosophila/metabolismo , Hemoglobinas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
AIM: To evaluate the salivary lactate dehydrogenase (LDH) levels in clinico-pathologically confirmed oral submucous fibrosis (OSMF), oral cancer and clinically diagnosed tobacco pouch keratosis patients. MATERIALS AND METHODS: A prospective, comparative study was carried out in a tertiary healthcare centre located in Loni from October 2013 to January 2014. A total of 120 patients were separated into 4 groups depending upon the clinical diagnosis as follows. Group I: healthy control (with no addictions and diseases). Group II: oral cancer. Group III: oral submucous fibrosis. Group IV: habitual tobacco chewers (tobacco addiction without any disease). Substantiation was done using biopsy. The samples were inspected for salivary LDH levels by the technique in line with the recommendations of the International Federation of Clinical Chemistry with the help of Erba Chem semi auto analyser. RESULTS: The mean salivary LDH levels in the control, oral cancer OSMF and habitual tobacco chewer group were 86.12 ± 7.05 IU/L, 592.09 ± 28.57 IU/L, 350.43 ± 5.90 IU/L and 125.19 ± 13.42 IU/L, respectively. Out of 4 groups, LDH activity was increased in saliva of patients with tobacco pouch keratosis, OSMF, and oral cancer consistently. Notable difference was found in the mean salivary levels of the above groups. Results were subjected to appropriate statistical analysis: one-way ANOVA, Student's unpaired t test for group-wise comparison followed by post hoc Tukey's test. CONCLUSION: We observed congruous higher levels of salivary LDH in oral precancer and cancer, and hence it could be a future marker.
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Neoplasias de la Boca , Fibrosis de la Submucosa Bucal , Biomarcadores , Humanos , L-Lactato Deshidrogenasa , Estudios Prospectivos , NicotianaRESUMEN
Small heat shock proteins (sHSPs) are one of the five families of proteins acting as molecular chaperone. sHSPs possess a universally conserved alpha-crystallin domain, hence, also known as alpha-crystallin family. Mycobacterium tuberculosis (MTB) is an etiological agent of tuberculosis, a disease claiming million of lives every year across the world. MTB has two sHSPs: sHSP16.3 (a 16.3 kDa protein) and Acr2 (a 17.8 kDa protein). Of these, sHSP16.3 has been reported to be crucial for survival of MTB during prolonged period of dormancy, in addition to indispensable role in its growth, virulence and cell wall thickening. Additionally, this mycobacterial protein is also beneficial for host as well. Due to strong immunogenic properties and consistent presence in patients sera, sHSP16.3 has largely been implicated in vaccine development and diagnosis of latent and active infections of MTB in the clinical cases of TB. Recently, our study provided the substantial evidence to exploit this mycobacterial protein as a good drug target for developing novel therapeutic intervention. In the present review, a comprehensive analysis of various attributes of sHSP16.3 has been done and major gaps in area have been highlighted for future course of action.
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Proteínas Bacterianas/metabolismo , Proteínas de Choque Térmico Pequeñas/metabolismo , Mycobacterium tuberculosis/metabolismo , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/genética , Proteínas de Choque Térmico Pequeñas/genética , Humanos , Mycobacterium tuberculosis/genética , Tuberculosis/diagnóstico , Tuberculosis/metabolismo , Tuberculosis/microbiología , alfa-Cristalinas/genética , alfa-Cristalinas/metabolismoRESUMEN
The present study was designed to investigate the solubility and penetrability of norfloxacin after the topical application of developed lipid-polymer hybrid nanoparticle (LPN) formulation. The core shell of the LPNs formulation was composed of poly (lactic-co-glycolic acid) that is highly lipophilic in nature, thus control the release of drug. The developed formulations were characterised for size, shape (transmission electron microscopy [TEM], scanning electron microscopy [SEM], and atomic force microscopy), entrapment efficiency, Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Moreover, in vitro skin permeation studies were performed to determine release profile of the drug. Norfloxacin loaded nanoparticles retained there antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa. Stability study was suggested that the suitable storage condition should be at 4 ± 2 °C/60 ± 5% RH for the LPNs. Therefore, these nanoparticles showed a safe and effective long-lasting approach for long treatment of bacterial infections due to burn.
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Infecciones Bacterianas/tratamiento farmacológico , Quemaduras/microbiología , Nanopartículas/química , Norfloxacino/administración & dosificación , Animales , Rastreo Diferencial de Calorimetría , Portadores de Fármacos/química , Pruebas de Sensibilidad Microbiana , Tamaño de la Partícula , Pseudomonas aeruginosa/efectos de los fármacos , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacosRESUMEN
BACKGROUND: Hemoglobins (Hbs) are evolutionarily conserved heme-containing metallo-proteins of the Globin protein family that harbour the characteristic "globin fold." Hemoglobins have been functionally diversified during evolution and their usual property of oxygen transport is rather a recent adaptation. Drosophila genome possesses three globin genes (glob1, glob2, and glob3), and we have reported earlier that adequate expression of glob1 is required for various aspects of development, as well as to regulate the cellular level of reactive oxygen species (ROS). The present study illustrates the explicit role of Drosophila globin1 in progression of oogenesis. RESULTS: We demonstrate a dynamic expression pattern of glob1 in somatic and germ cell derivatives of developing egg chambers during various stages of oogenesis, which largely confines around the F-actin-rich cellular components. Reduced expression of glob1 leads to various types of abnormalities during oogenesis, which were primarily mediated by the inappropriately formed F-actin-based cytoskeleton. Our subsequent analysis in the somatic and germ line clones shows cell autonomous role of glob1 in the maintenance of the integrity of F-actin-based cytoskeleton components in the somatic and germ cell derivatives. CONCLUSIONS: Our study establishes a novel role of glob1 in maintenance of F-actin-based cytoskeleton during progression of oogenesis in Drosophila. Developmental Dynamics 245:1048-1065, 2016. © 2016 Wiley Periodicals, Inc.
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Citoesqueleto/metabolismo , Proteínas de Drosophila/metabolismo , Hemoglobinas/metabolismo , Oogénesis/fisiología , Actinas/metabolismo , Animales , Citoesqueleto/genética , Drosophila/embriología , Drosophila/metabolismo , Proteínas de Drosophila/genética , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Hemoglobinas/genética , Inmunohistoquímica , Hibridación in Situ , Etiquetado Corte-Fin in Situ , Oogénesis/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND & OBJECTIVES: Dental caries is an infectious, transmissible disease. Maternal transfer of mutans streptococci (MS) has been a subject of research. The aim of this study was to evaluate the transmission of MS from mother to children through genetic analysis. METHODS: Thirty mother-child pairs were included and divided into three groups according to the age of the children. Saliva samples were collected and MS colonies from each mother-child pair were isolated. After inoculation and incubation, MS colonies were submitted to amplification technique by polymerase chain reaction (PCR) for identification and arbitrarily primed PCRs (AP-PCRs) to determine various MS genotypes. RESULTS: From birth to six months of age, 30 per cent of children exhibited MS colonization, and by the age of 30 months, 100 per cent harboured the bacteria (P < 0.001). Factors associated with MS colonization were eruption of teeth (P < 0.001), feeding habits with mean colony count being significantly lower in breast-fed as compared to bottle-fed children (P < 0.001) and a significant association between mean MS count of child and mother's practice of sharing spoon with child (P < 0.001). The AP-PCR fingerprinting profile analysis showed 17 MS groups (clusters) containing identical or highly related isolates in mother-child pairs with a high level of similarity (77.27 %). INTERPRETATION & CONCLUSIONS: The presence of matching MS genotypes suggested vertical transmission from mothers to children. Feeding habits, gum cleaning and number of erupted teeth in children had significant effect on MS colonization. There is a need to develop strategies to present MS colonization in children.
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ADN Bacteriano/aislamiento & purificación , Caries Dental/microbiología , Transmisión Vertical de Enfermedad Infecciosa , Streptococcus mutans/aislamiento & purificación , Adulto , ADN Bacteriano/genética , Caries Dental/genética , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Relaciones Madre-Hijo , Saliva/microbiología , Streptococcus mutans/genéticaRESUMEN
Biological significance of the globin protein family could be ascertained by their conservation through archaea to human. Globin(s) have been "classically" studied as oxygen binding protein(s), with recent implications in a host of other physiological functions. Drosophila melanogaster possesses three globin genes (glob1, glob2, glob3) located at different cytogenetic positions. We have performed a comprehensive investigation on the cellular expression profile and functional relevance of glob1 in Drosophila development. A profound level of maternally contributed glob1 gene products was found during early embryogenesis. Subsequently, commencement of zygotic transcription leads to its strong expression in somatic muscles, gut primordia, fat bodies, tracheal cells, etc. Similarly, dynamic expression of glob1 was evident in most of the larval tissues, interestingly with high expression in dividing cells. Reduced expression of glob1 leads to various impairments and lethality during embryogenesis and larval development. A substantial increase in level of cellular ROS was also evident due to reduced expression of glob1 which consequently leads to locomotor impairment and early aging in surviving adult flies. To best of our knowledge, this is the first report which demonstrates that in addition to oxygen management, globin gene(s) are also involved in regulating various aspects of development in Drosophila.
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Proteínas de Drosophila/biosíntesis , Drosophila melanogaster/fisiología , Globinas/biosíntesis , Estrés Oxidativo/fisiología , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/metabolismo , Desarrollo Embrionario , Femenino , Regulación del Desarrollo de la Expresión Génica , Globinas/genética , Hemoglobinas , Larva , Masculino , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Curcumin is a major bioactive compound of turmeric that exerts its anti-inflammatory effects by suppressing the many pro-inflammatory cytokines and chemokines in a number of cell types and pathologic conditions. Interleukin-18 (IL-18) is a novel pro-inflammatory cytokine which plays an important role not only in generating Th1 responses but also in inducing severe inflammatory reactions. As curcumin induced inhibition of IL-18 production in keratinocytes and mice is well known, effect of curcumin on IL-18 release in macrophages remains unknown. Hence, this present study has been designed to evaluate the effect of curcumin on IL-18 production and necrotic cell death in murine macrophages-like cells treated with or without lipopolysaccharide (LPS). The IL-18 secretion in cell culture supernatants was assayed by enzyme-linked immunosorbent assay and cytotoxicity was determined by lactate dehydrogenase release assay. Our results demonstrate that curcumin significantly inhibited the production of pro-inflammatory cytokine IL-18 in E.coli LPS stimulated murine macrophage-like cells RAW264.7 in a concentration-dependent manner. Interestingly, curcumin had no cytotoxic effect on murine macrophage-like cells. Our findings suggest that curcumin may be used as a potential therapeutic agent for the treatment of inflammatory diseases.
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In the present study, we used crystal structure of mycobacterial pantothenate synthetase (PS) bound with 2-(2-(benzofuran-2-ylsulfonylcarbamoyl)-5-methoxy-1H-indol-1-yl) acetic acid inhibitor for virtual screening of antitubercular compound database to identify new scaffolds. One of the identified lead was modified synthetically to obtain thirty novel analogues. These synthesized compounds were evaluated for Mycobacterium tuberculosis (MTB) PS inhibition study, in vitro antimycobacterial activities and cytotoxicity against RAW 264.7 cell line. Among the compounds tested, N'-(1-naphthoyl)-2-methylimidazo[1,2-a]pyridine-3-carbohydrazide (5b) was found to be the most active compound with IC50 of 1.90 ± 0.12 µM against MTB PS, MIC of 4.53 µM against MTB with no cytotoxicity at 50 µM. The binding affinity of the most potent inhibitor 5b was further confirmed biophysically through differential scanning fluorimetry.
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Amidas/química , Antituberculosos/química , Proteínas Bacterianas/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/enzimología , Péptido Sintasas/antagonistas & inhibidores , Amidas/síntesis química , Amidas/farmacología , Animales , Antituberculosos/síntesis química , Antituberculosos/farmacología , Proteínas Bacterianas/metabolismo , Sitios de Unión , Dominio Catalítico , Línea Celular , Supervivencia Celular/efectos de los fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Simulación de Dinámica Molecular , Péptido Sintasas/metabolismo , Piridinas/química , Relación Estructura-ActividadRESUMEN
Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.
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Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Micobioma , Humanos , Micobioma/fisiología , Disbiosis/terapia , Disbiosis/microbiología , Ecosistema , Enfermedades Inflamatorias del Intestino/terapia , Enfermedades Inflamatorias del Intestino/microbiologíaRESUMEN
High-altitude regions, cold deserts, permafrost regions, and the polar region have some of the severest cold conditions on earth and pose immense perils of cold injuries to exposed individuals. Accidental and unintended exposures to severe cold, either unintentionally or due to occupational risks, can greatly increase the risk of serious conditions including hypothermia, trench foot, and cold injuries like frostbite. Cold-induced vasoconstriction and intracellular/intravascular ice crystal formation lead to hypoxic conditions at the cellular level. The condition is exacerbated in individuals having inadequate and proper covering and layering, particularly when large area of the body are exposed to extremely cold environments. There is a paucity of preventive and therapeutic pharmacological modalities that have been explored for managing and treating cold injuries. Given this, an efficient modality that can potentiate the healing of frostbite was investigated by studying various complex pathophysiological changes that occur during severe cold injuries. In the current research, we report the effectiveness and healing properties of a standardized formulation, i.e., a herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF), on frostbite. The intricate mechanistic pathways modulated by the novel formulation have been elucidated by studying the pathophysiological sequelae that occur following severe cold exposures leading to frostbite. The results indicate that n-HPTF ameliorates the outcome of frostbite, as it activates positive sensory nerves widely distributed in the epidermis transient receptor potential vanilloid 1 (TRPV1), significantly (p < 0.05) upregulates cytokeratin-14, promotes angiogenesis (VEGF-A), prominently represses the expression of thromboxane formation (TXA2), and significantly (p < 0.05) restores levels of enzymatic (glutathione reductase, superoxide dismutase, and catalase) and nonenzymatic antioxidants (glutathione). Additionally, n-HPTF attenuates oxidative stress and the expression of inflammatory proteins PGF-2α, NFκB-p65, TNF-α, IL-6, IL-1ß, malondialdehyde (MDA), advanced oxidative protein products (AOPP), and protein carbonylation (PCO). Masson's Trichrome staining showed that n-HPTF stimulates cellular proliferation, and increases collagen fiber deposition, which significantly (p < 0.05) promotes the healing of frostbitten tissue, as compared to control. We conclude that protection against severe cold injuries by n-HPTF is mediated via modulation of pathways involving TRPV1, VEGF-A, TXA2, redox homeostasis, and inflammatory cascades. The study is likely to have widespread implications for the prophylaxis and management of moderate-to-severe frostbite conditions.
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Homeostasis , Poloxámero , Polietilenglicoles , Canales Catiónicos TRPV , Factor A de Crecimiento Endotelial Vascular , Factor A de Crecimiento Endotelial Vascular/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Poloxámero/química , Poloxámero/farmacología , Polietilenglicoles/química , Polietilenglicoles/farmacología , Homeostasis/efectos de los fármacos , Oxidación-Reducción , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ratas , Ensayo de Materiales , Lesión por Frío/metabolismo , Lesión por Frío/tratamiento farmacológico , Tamaño de la Partícula , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Liposomas/química , Humanos , Administración Tópica , Congelación de Extremidades/metabolismo , Congelación de Extremidades/tratamiento farmacológicoRESUMEN
Delivering drugs to the brain is a complex challenge in medical research, particularly for disorders like Alzheimer's and Parkinson's. The blood-brain barrier restricts the entry of many therapeutic molecules, hindering their effectiveness. Nanoparticles, a potential solution, face issues like toxicity and limited approvals. A new avenue explores the use of small extracellular vesicles (sEVs), i.e., exosomes, as natural carriers for drug delivery. sEVs, tiny structures below 150 nm, show promise due to their minimal immune response and ability to precisely deliver drugs. This review focuses on the potential of sEVs-based drug delivery systems for treating neurological disorders, brain cancers, and other brain-related issues. Notably, bioengineered sEVs-carrying therapeutic compounds exhibit promise in early studies. The unique features of sEVs, such as their small size and natural properties, position them as candidates to overcome challenges in drug delivery to the brain. Ongoing clinical trials and research into sEVs behavior within the body further highlight their potential for revolutionizing drug delivery and addressing complex brain conditions.