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1.
J Physiol ; 602(7): 1405-1426, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38457332

RESUMO

Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspective on how peripheral activity shapes central nervous system function.


Assuntos
Núcleos Talâmicos , Tálamo , Ratos , Animais , Tálamo/fisiologia , Núcleos Talâmicos/fisiologia , Neurônios/fisiologia , Dor , Face , Córtex Somatossensorial/fisiologia
2.
STAR Protoc ; 5(2): 102972, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38502685

RESUMO

Studies on sensory information processing typically focus on whisker-related tactile information, overlooking the question of how sensory inputs from other body areas are processed at cortical levels. Here, we present a protocol for stimulating specific rodent limb receptive fields while recording in vivo somatosensory-evoked activity. We describe steps for localizing cortical-hindlimb coordinates using acute peripheral stimulation, electrode placement, and the application of electrical stimulation. This protocol overcomes the challenge of inducing a reproducible and consistent stimulation of specific limbs. For complete details on the use and execution of this protocol, please refer to Miguel-Quesada et al.1.

3.
Antibiotics (Basel) ; 13(2)2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38391568

RESUMO

Chili powder is an important condiment around the world. However, according to various reports, the presence of pathogenic microorganisms could present a public health risk factor during its consumption. Therefore, microbiological quality assessment is required to understand key microbial functional traits, such as antibiotic resistance genes (ARGs). In this study, metagenomic next-generation sequencing (mNGS) and bioinformatics analysis were used to characterize the comprehensive profiles of the bacterial community and antibiotic resistance genes (ARGs) in 15 chili powder samples from different regions of Mexico. The initial bacterial load showed aerobic mesophilic bacteria (AMB) ranging between 6 × 103 and 7 × 108 CFU/g, sporulated mesophilic bacteria (SMB) from 4.3 × 103 to 2 × 109 CFU/g, and enterobacteria (En) from <100 to 2.3 × 106 CFU/g. The most representative families in the samples were Bacillaceae and Enterobacteriaceae, in which 18 potential pathogen-associated species were detected. In total, the resistome profile in the chili powder contained 68 unique genes, which conferred antibiotic resistance distributed in 13 different classes. Among the main classes of antibiotic resistance genes with a high abundance in almost all the samples were those related to multidrug, tetracycline, beta-lactam, aminoglycoside, and phenicol resistance. Our findings reveal the utility of mNGS in elucidating microbiological quality in chili powder to reduce the public health risks and the spread of potential pathogens with antibiotic resistance mechanisms.

4.
Injury ; 54 Suppl 6: 110720, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38143143

RESUMO

INTRODUCTION: Open tibial plateau fractures are complex injuries that require specialized management to prevent complications. The objective of this study was to compare the infection risk and functional outcomes between open and closed tibial plateau fractures. MATERIALS AND METHODS: In this multicenter cohort study the propensity score matching was used to pair participants according to age, sex, and Schatzker classification. 190 patients were followed for 1 year postoperatively. The Fracture-Related Infection (FRI) Consensus Group criteria was used to diagnose infection. Knee functionality was measured using the Oxford Knee Score scale (OKS). RESULTS: The proportion of open fractures was 5.1%, and the overall incidence rate of FRI was 8% with 14% of them represented by open fractures and 4% for closed fractures (p = 0.014). Open fractures were found to be a risk factor associated with FRI, with a 5.48 times higher probability of FRI than closed fractures (odds ratio 5.41, 95% confidence interval [CI] 1.55-18.85). Among the study population, 50% had satisfactory functional outcomes of the knee (median OKS 45, IQR = 3). The median OKS was 44 (IQR = 11) in open fractures and 46 (IQR = 7) in closed ones (p = 0.03). Multivariate analysis showed that the OKS was 3 points lower for open fractures (95% CI -5.530--0.478) than closed ones, and the score was 9.7 points lower for FRI. CONCLUSION: Open TPF is a risk factor that increases the probability of fracture related infections. Functional outcomes were excellent for both open and closed TPF, with a slight difference numerical that was under the minimal clinical difference (MCID). The presence of FRI significantly decreases the functional outcome.


Assuntos
Fraturas Fechadas , Fraturas Expostas , Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Fraturas Expostas/cirurgia , Estudos de Coortes , Fixação Interna de Fraturas , Fraturas da Tíbia/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Children (Basel) ; 10(12)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38136033

RESUMO

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). METHODOLOGY: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). RESULTS: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27-31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. CONCLUSIONS: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS.

6.
Biomedicines ; 11(11)2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38002094

RESUMO

The transition metal characteristics of iron allow it to play a fundamental role in several essential aspects of human life such as the transport of oxygen through hemoglobin or the transport of electrons in the mitochondrial respiratory chain coupled to the synthesis of ATP. However, an excess or deficiency of iron is related to certain pathologies. The maintenance of iron homeostasis is essential to avoid certain pathologies related to iron excess or deficiency. The existence of iron deposits in postmortem tissues of Parkinson's patients has been interpreted as evidence that iron plays a fundamental role in the degenerative process of the nigrostriatal system in this disease. The use of iron chelators has been successful in the treatment of diseases such as transfusion-dependent thalassemia and pantothenate kinase-associated neurodegeneration. However, a clinical study with the iron chelator deferiprone in patients with Parkinson's disease has not shown positive effects but rather worsened clinical symptoms. This suggests that iron may not play a role in the degenerative process of Parkinson's disease.

7.
Chem Sci ; 14(41): 11389-11401, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37886106

RESUMO

Pathway complexity results in unique materials from the same components according to the assembly conditions. Here a chiral acyl-semicarbazide gelator forms three different gels of contrasting fibre morphology (termed 'gelmorphs') as well as lyotropic liquid crystalline droplets depending on the assembly pathway. The gels have morphologies that are either hyperhelical (HH-Gel), tape-fibre (TF-Gel) or thin fibril derived from the liquid crystalline phase (LC-Gels) and exhibit very different rheological properties. The gelator exists as three slowly interconverting conformers in solution. All three gels are comprised of an unsymmetrical, intramolecular hydrogen bonded conformer. The kinetics show that formation of the remarkable HH-Gel is cooperative and is postulated to involve association of the growing fibril with a non-gelling conformer. This single molecule dynamic conformational library shows how very different materials with different morphology and hence very contrasting materials properties can arise from pathway complexity as a result of emergent interactions during the assembly process.

8.
Biomed Pharmacother ; 168: 115712, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37871556

RESUMO

BACKGROUND: In both clinical and experimental trials, pirfenidone (PFD) showed anti-inflammatory and antifibrogenic effects. Considering the wide variation in hepatic functional reserve in patients with cirrhosis, we decided to learn more about the pharmacokinetics of a new formulation of prolonged release PFD in this population (PR-PFD), focusing on assessing changes on AUC0-∞, AUC0-t, and Cmax. METHODS: In this study, 24 subjects with cirrhosis were included: eight subjects with mild liver impairment (Child-Pugh A) and eight with moderate liver impairment (Child-Pugh B), and a third group of eight age-matched subjects without fibrosis. All participants were under fasting conditions before receiving orally two 600-mg tablets of a prolonged-release formulation of pirfenidone (PR-PFD) and remained in the clinical unit for 36 h after PR-PFD administration. Serial blood samples were collected after dosing (0.5-36 h). A validated high-performance liquid chromatography-mass spectrometry method was used to determine PFD plasma concentrations. RESULTS: The exposure to PR-PFD was 3.6- and 4.4-fold greater in subjects with Child-Pugh A and Child-Pugh B than in subjects without cirrhosis, and Cmax was 1.6- and 1.8-fold greater in subjects with Child-Pugh B and Child-Pugh-A than in patients without cirrhosis, without significant differences between the two cirrhotic groups. PFD was well tolerated. CONCLUSION: The pharmacokinetic parameters of PR-PFD are significantly modified in patients with cirrhosis compared with those in controls, indicating that liver impairment should be considered in clinical practice.


Assuntos
Cirrose Hepática , Hepatopatias , Humanos , Cirrose Hepática/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Piridonas/uso terapêutico , Área Sob a Curva
10.
Chem Commun (Camb) ; 59(79): 11753-11766, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37703047

RESUMO

The recent development and implementation of copper-based metal-organic frameworks in biological applications are reviewed. The advantages of the presence of copper in MOFs for relevant applications such as drug delivery, cancer treatment, sensing, and antimicrobial are highlighted. Advanced composites such as MOF-polymers are playing critical roles in developing materials for specific applications.

11.
Rev. colomb. gastroenterol ; 38(3)sept. 2023.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1535921

RESUMO

Aim: To establish the relationship between consuming foods considered risk factors for gastric cancer and trophic changes in gastric mucosa. Materials and methods: Cross-sectional study. We included patients older than 18 admitted for upper GI endoscopy with biopsies who adequately answered a survey of personal history and eating habits. Those with a history of gastric cancer or gastric surgical resection for any reason were excluded. The association between feeding variables and trophic changes in the gastric mucosa was estimated. Results: In a population of 1,096 patients, the average age was 51 years (standard deviation [SD]: 15.5), and 59% were women. Trophic changes in the gastric mucosa were identified in 173 patients (15.8%). No statistical association was found between the independent variables of eating habits, obesity, and positive Helicobacter pylori versus the variable "trophic changes," unlike the variable "family history of gastric cancer" (odds ratio [OR]: 1.49 95% confidence interval [CI]: 1.03-2.17, p = 0.036). One case of high-grade dysplasia was detected in the study population (0.91 cases in 1,000 patients). Conclusions: No association was established between eating habits and trophic changes in the gastric mucosa in the studied population. A family history of gastric cancer is a statistically significant risk factor for developing atrophy, metaplasia, or dysplasia changes.


Objetivo: establecer la relación entre el consumo de alimentos considerados como factores de riesgo para cáncer gástrico y la presencia de cambios tróficos de la mucosa gástrica. Materiales y métodos: estudio de corte transversal. Se incluyeron los pacientes mayores de 18 años admitidos para realización de endoscopia digestiva superior con toma de biopsias que respondieron adecuadamente una encuesta de antecedentes personales y hábitos de alimentación. Se excluyeron aquellos con antecedente de cáncer gástrico o resección quirúrgica gástrica por cualquier motivo. Se estimó la asociación entre las variables de alimentación y la presencia de cambios tróficos de la mucosa gástrica. Resultados: en una población de 1096 pacientes, el promedio de la edad fue 51 años (desviación estándar [DE]: 15,5), y correspondió en un 59% a mujeres. Se identificaron cambios tróficos de la mucosa gástrica en 173 pacientes (15,8%). No se obtuvo asociación estadística entre las variables independientes de hábitos de alimentación, obesidad y Helicobacter pylori positivo frente a la variable "cambios tróficos", a diferencia de la variable "antecedente familiar de cáncer gástrico" (odds ratio [OR]: 1,49; intervalo de confianza [IC] 95%: 1,03-2,17; p = 0,036). Se obtuvo 1 caso de displasia de alto grado en la población estudiada (0,91 casos en 1000 pacientes). Conclusiones: no se estableció una asociación entre los hábitos de alimentación y la presencia de cambios tróficos de la mucosa gástrica en la población estudiada. El antecedente familiar de cáncer gástrico se muestra como un factor de riesgo estadísticamente significativo para el desarrollo de cambios de atrofia, metaplasia o displasia.

12.
Exp Neurol ; 369: 114504, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37591355

RESUMO

The complete or partial damage of ascending somatosensory pathways produced by a spinal cord injury triggers changes in the somatosensory cortex consisting in a functional expansion of activity from intact cortical regions towards deafferented ones, a process known as cortical reorganization. However, it is still unclear whether cortical reorganization depends on the severity of the spinal cord damage or if a spinal cord injury always leads to a similar cortical reorganization process in the somatosensory cortex. To answer these open questions in the field, we obtained longitudinal somatosensory evoked responses from bilateral hindlimb and forelimb cortex from animals with chronic full-transection or contusive spinal cord injury at thoracic level (T9-T10) to induce sensory deprivation of hindlimb cortex while preserving intact the forelimb cortex. Electrophysiological recordings from the four locations were obtained before lesion and weekly for up to 4 weeks. Our results show that cortical reorganization depends on the type of spinal cord injury, which tends to be more bilateral in full transection while is more unilateral in the model of contusive spinal cord injury. Moreover, in full transection of spinal cord, the deafferented and intact cortex exhibited similar increments of somatosensory evoked responses in both models of spinal cord injury - a feature observed in about 80% of subjects. The other 20% were unaffected by the injury indicating that cortical reorganization does not undergo in all subjects. In addition, we demonstrated an increased probability of triggered up-states in animals with spinal cord injury. This data indicates increased cortical excitability that could be proposed as a new feature of cortical reorganization. Finally, decreased levels of GABA marker GAD67 across cortical layers were only found in those animals with increased somatosensory evoked responses, but not in the unaffected population. In conclusion, cortical reorganization depends on the types of spinal cord injuries, and suggest that the phenomenon is strongly determined by cortical circuits. Moreover, changes in GABAergic transmission at the deprived cortex may be considered one of the mechanisms underlying the process of cortical reorganization and increased excitability.

13.
Cell Rep ; 42(8): 112950, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37543946

RESUMO

Cortical neuron-astrocyte communication in response to peripheral sensory stimulation occurs in a topographic-, frequency-, and intensity-dependent manner. However, the contribution of this functional interaction to the processing of sensory inputs and consequent behavior remains unclear. We investigate the role of astrocytes in sensory information processing at circuit and behavioral levels by monitoring and manipulating astrocytic activity in vivo. We show that astrocytes control the dynamic range of the cortical network activity, optimizing its responsiveness to incoming sensory inputs. The astrocytic modulation of sensory processing contributes to setting the detection threshold for tactile and thermal behavior responses. The mechanism of such astrocytic control is mediated through modulation of inhibitory transmission to adjust the gain and sensitivity of responding networks. These results uncover a role for astrocytes in maintaining the cortical network activity in an optimal range to control behavior associated with specific sensory modalities.


Assuntos
Astrócitos , Córtex Somatossensorial , Astrócitos/fisiologia , Vias Neurais , Cálcio/metabolismo , Neurônios/fisiologia , Eletrofisiologia , Animais , Camundongos , Córtex Somatossensorial/citologia , Córtex Somatossensorial/fisiologia , Percepção Olfatória , Percepção do Tato
14.
Microorganisms ; 11(7)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37512930

RESUMO

Kosakonia cowanii strain Ch1 was isolated from Mexican chili powder, and the genome was sequenced. The genome was 4,765,544 bp in length, with an average G + C content of 56.22%, and a plasmid (pCh1) of 128,063 bp with an average G + C content of 52.50%. A phylogenetic analysis revealed a close relation with pathogenic strains; nevertheless, some virulence-related genes were absent, and this genetic characteristic may explain the fact that K. cowanii Ch1 behaved as a non-pathogenic strain when infection assays were performed on the leaves and fruits of Capsicum annuum L. Surprisingly, we observed that this bacterial strain had the ability to spread throughout serrano pepper seeds. Furthermore, K. cowanii Ch1 was evaluated for the production of volatile organic compounds (VOCs) against fungal pathogens, and the results showed that Alternaria alternata and Sclerotium rolfsii were inhibited in a radial mycelial growth assay by a mean rate of 70% and 64%, while Fusarium oxysporum was inhibited by only approximately 10%. Based on the headspace solid-phase microextraction combined with the gas chromatography mass spectrometry (HS-SPME-GC-MS), 67 potential VOCs were identified during the fermentation of K. cowanii Ch1 in TSA medium. From these VOCs, nine main compounds were identified based on relative peak area: dodecanoic acid; 3-hydroxy ethanol; 1-butanol-3-methyl; acetaldehyde; butanoic acid, butyl ester; cyclodecane; 2-butanone, 3-hydroxy; disulfide, dimethyl and pyrazine-2,5-dimethyl. Our findings show the potential of K. cowanii Ch1 for the biocontrol of fungal pathogens through VOCs production and reveal additional abilities and metabolic features as beneficial bacterial specie.

15.
bioRxiv ; 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37503130

RESUMO

Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which the astrocyte calcium signal plays a crucial role. Synaptically-evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e., calcium surge. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because a single astrocyte may contact ~100,000 synapses, the control of the intracellular calcium signal propagation may have relevant consequences on brain function by regulating the spatial range of astrocyte neuromodulation of synapses. Yet, the properties governing the spatial dynamics of the astrocyte calcium signal remains poorly defined. Imaging subcellular responses of cortical astrocytes to sensory stimulation in mice, we show that sensory-evoked astrocyte calcium responses originated and remained localized in domains of the astrocytic arborization, but eventually propagated to the entire cell if a spatial threshold of >23% of the arborization being activated was surpassed. Using transgenic IP3R2-/- mice, we found that type-2 IP3 receptors were necessary for the generation of the astrocyte calcium surge. We finally show using in situ electrophysiological recordings that the spatial threshold of the astrocyte calcium signal consequently determined the gliotransmitter release. Present results reveal a fundamental property of astrocyte calcium physiology, i.e., a spatial threshold for the astrocyte intracellular calcium signal propagation, which depends on astrocyte intrinsic properties and governs the astrocyte integration of local synaptic activity and the subsequent neuromodulation.

16.
Microorganisms ; 11(6)2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37375088

RESUMO

Heavy metal pollution is a severe concern worldwide, owing to its harmful effects on ecosystems. Phytoremediation has been applied to remove heavy metals from water, soils, and sediments by using plants and associated microorganisms to restore contaminated sites. The Typha genus is one of the most important genera used in phytoremediation strategies because of its rapid growth rate, high biomass production, and the accumulation of heavy metals in its roots. Plant growth-promoting rhizobacteria have attracted much attention because they exert biochemical activities that improve plant growth, tolerance, and the accumulation of heavy metals in plant tissues. Because of their beneficial effects on plants, some studies have identified bacterial communities associated with the roots of Typha species growing in the presence of heavy metals. This review describes in detail the phytoremediation process and highlights the application of Typha species. Then, it describes bacterial communities associated with roots of Typha growing in natural ecosystems and wetlands contaminated with heavy metals. Data indicated that bacteria from the phylum Proteobacteria are the primary colonizers of the rhizosphere and root-endosphere of Typha species growing in contaminated and non-contaminated environments. Proteobacteria include bacteria that can grow in different environments due to their ability to use various carbon sources. Some bacterial species exert biochemical activities that contribute to plant growth and tolerance to heavy metals and enhance phytoremediation.

17.
Ecol Evol ; 13(6): e10143, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37351480

RESUMO

The Magellanic sub-Antarctic Forest is home to the world's southernmost avian community and is the only Southern Hemisphere analogue to Northern Hemisphere temperate forests at this latitude. This region is considered among the few remaining pristine areas of the world, and shifts in environmental conditions are predominantly driven by climate variability. Thus, understanding climate-driven demographic processes is critical for addressing conservation issues in this system under future climate change scenarios. Here, we describe annual survival patterns and their association with climate variables using a 20-year mark-recapture data set of five forest bird species in the Cape Horn Biosphere Reserve. We develop a multispecies hierarchical survival model to jointly explore age-dependent survival probabilities at the community and species levels in a group of five forest passerines. At the community level, we assess the association of migratory behavior and body size with survival, and at the species level, we investigate the influence of local and regional climatic variables on temporal variations of survival. We found a positive effect of precipitation and a negative effect of El Niño Southern Oscillation on juvenile survival in the white-crested Elaenia and a consistent but uncertain negative effect of temperature on survival in juveniles and 80% of adults. We found only a weak association of climate variables with survival across species in the community and no temporal trends in survival for any of the species in either age class, highlighting apparent stability in these high austral latitude forests. Finally, our findings provide an important resource of survival probabilities, a necessary input for assessing potential impacts of global climate change in this unique region of the world.

18.
Infect Genet Evol ; 113: 105474, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37356747

RESUMO

Despite the high incidence of urogenital carcinoma (UGC) in California sea lions stranded along California, no UGC has been reported in other areas of their distribution; however, cell morphologies typical of premalignant states have been found. Risk factors for UGC include high of organochlorines and infection with a gammaherpesvirus, OtHV-1, but the importance of the bacteriome for epithelial status remains unknown. We characterized the genital bacteriome of adult female California sea lions along their distribution in the Gulf of California and examined whether the diversity and abundance of the bacteriome varied spatially, whether there were detectable differences in the bacteriome between healthy and altered epithelia, and whether the bacteriome was different in California sea lions infected with OtHV-1 or papillomavirus. We detected 2270 ASVs in the genital samples, of which 35 met the criteria for inclusion in the core bacteriome. Fusobacteriia and Clostridia were present in all samples, at high abundances, and Actinobacteria, Alphaproteobacteria, and Campylobacteria were also well-represented. Alpha diversity and abundance of the California sea lion genital bacteriome varied geographically. The abundance of bacterial ASVs varied depending on the genital epithelial status and inflammation, with differences driven by classes Fusobacteriia, Clostridia, Campylobacteria and Alphaproteobacteria. Alpha diversity and abundance were lowest in samples in which OtHV-1 was detected, and highest those with papillomavirus. Our study is the first investigation of how the bacteriome is related to epithelial status in a wild marine species prone to developing cancer.


Assuntos
Gammaherpesvirinae , Leões-Marinhos , Neoplasias Urogenitais , Animais , Feminino , Leões-Marinhos/microbiologia , Disbiose/veterinária , Neoplasias Urogenitais/epidemiologia , Bactérias
19.
Proteomics ; 23(16): e2300041, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37140101

RESUMO

Pancreatic cancer is one of the most lethal cancer types and is becoming a leading cause of cancer-related deaths. The limited benefit offered by chemotherapy agents has propelled the search for alternative approaches that target specific molecular drivers of cancer growth and progression. Mutant KRas and effector pathways Raf/MEK/ERK and PI3K/Akt are key players in pancreatic cancer; however, preclinical studies have shown adaptive tumour response to combined MEK and PI3K kinase inhibition leading to treatment resistance. There is a critical unmet need to decipher the molecular basis underlying adaptation to this targeted approach. Here, we aimed to identify common protein expression alterations associated with adaptive resistance in KRas-mutant pancreatic cancer cells, and test if it can be overcome by selected already available small molecule drugs. We found a group of 14 proteins with common expression change in resistant cells, including KRas, caveolin-1, filamin-a, eplin, IGF2R and cytokeratins CK-8, -18 and -19. Notably, several proteins have previously been observed in pancreatic cancer cells with intrinsic resistance to the combined kinase inhibition treatment, suggesting a proteomic signature. We also found that resistant cells are sensitive to small molecule drugs ERK inhibitor GDC-0994, S6K1 inhibitor DG2 and statins.


Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteômica , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Mutação , Neoplasias Pancreáticas
20.
Int Immunopharmacol ; 120: 110376, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37244118

RESUMO

Monoclonal antibodies (mAbs) have been used in the development of immunotherapies that target a variety of diseases, such as cancer, autoimmune diseases, and even viral infections; they play a key role in immunization and are expected after vaccination. However, some conditions do not promote the development of neutralizing antibodies. Production and use of mAbs, generated in biofactories, represent vast potential as aids in immunological responses when the organism cannot produce them on their own, these convey unique specificity by recognizing and targeting specific antigen. Antibodies can be defined as heterotetrametric glycoproteins of symmetric nature, and they participate as effector proteins in humoral responses. Additionally, there are different types of mAbs (murine, chimeric, humanized, human, mAbs as Antibody-drug conjugates and bispecific mAbs) discussed in the present work. When these molecules are produced in vitro as mAbs, several common techniques, such as hybridomas or phage display are used. There are several preferred cell lines that function as biofactories, for the production of mAbs, the selection of which rely on the variation of adaptability, productivity and both phenotypic and genotypic shifts. After the cell expression systems and culture techniques are used, there are diverse specialized downstream processes to achieve desired yield and isolation as well as product quality and characterization. Novel perspectives regarding these protocols represent a potential improvement for mAbs high-scale production.


Assuntos
Anticorpos Biespecíficos , Anticorpos Monoclonais , Humanos , Animais , Camundongos , Anticorpos Monoclonais/uso terapêutico , Hibridomas/metabolismo , Imunização , Vacinação , Anticorpos Neutralizantes , Anticorpos Antivirais
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