Embryo development is impaired by sperm mitochondrial-derived ROS

BACKGROUND: Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. RESULTS: We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. CONCLUSION: Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.

Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors / 药学学报

The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Research progress on the regulation of intestinal flora and effect on intestinal absorption and transport by TCM components / 药学实践杂志

The domestic and international research progress on the regulation of gut microbiota by Traditional Chinese Medicine (TCM) ingredients and their impact on intestinal absorption and transportation were summarized, which provided assistance for subsequent clinical rational drug use targeting gut microbiota. Literature on the relationship between gut microbiota and intestinal absorption and transportation in recent years were reviewed and analyzed, and the mechanism of TCM ingredients regulating gut microbiota on drug absorption and transportation was elucidated. Research has found that TCM ingredients alter gut microbiota, thereby affecting intestinal barrier function and absorption of transport proteins, which is of great significance for rational clinical medication.

Golgi Transport 1A Promotes Cell Proliferation and Metastasis of Papillary Thyroid Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the expression level of Golgi transport 1A （GOLT1A） in thyroid carcinoma and its effects on the proliferation， migration， invasion， and epithelial-mesenchymal transition （EMT） of thyroid carcinoma cells. MethodsThe expression of GOLT1A in thyroid carcinoma was analyzed online by tumor immune estimation resource （TIMER）， the University of Alabama at Birmingham cancer data analysis portal （UALCAN）， gene expression profiling interactive analysis 2 （GEPIA2）. The expression level of GOLT1A in thyroid carcinoma cells was detected by real-time fluorescence quantitative polymerase chain reaction （RTFQ-PCR） and western blot. Cell counting kit-8 （CCK-8） assay， colony formation assay， and transwell assay were used to detect the effects of GOLT1A expression on the proliferation， migration， and invasion of thyroid carcinoma cells. Western blot assay was used to detect the effect of GOLT1A on the expression of EMT-related genes including E-cadherin， vimentin， and N-cadherin. ResultsThe online analysis of GEPIA2， TIMER， and UALCAN showed that the expression of GOLT1A was higher in thyroid carcinoma than in normal tissues， and the expression of GOLT1A in thyroid carcinoma cells was significantly higher than in normal control cells. Knockdown of GOLT1A inhibited TPC1 cell proliferation， migration， and invasion. The expression of E-cadherin increased and the expressions of N-cadherin and vimentin decreased in GOLT1A knockdown TPC1 cells. Overexpression of GOLT1A promoted BCPAP cell proliferation， migration， and invasion. The expression of E-cadherin decreased and the expressions of N-cadherin and vimentin increased in GOLT1A overexpression BCPAP cells. ConclusionGOLT1A is highly expressed in thyroid carcinoma and can promote the proliferation， migration， and invasion of thyroid carcinoma cells.

Escala de Respuestas Emocionales por Estrés al Traslado en Transporte Público / Scale of Emotional Responses due to Commuting Stress in Public Transport

Resumen El traslado cotidiano entre la casa y el trabajo demanda un importante uso de recursos personales y puede llegar a ser estresante. El objetivo fue construir y evaluar una escala de respuestas emocionales por el estrés en el traslado en transporte público para la Zona Metropolitana del Valle de México de manera exploratoria. Método: Se realizó un estudio cualitativo a través de entrevistas semi estructuradas con el propósito de identificar emociones asociadas a la experiencia de estrés por el traslado para desarrollar los reactivos de acuerdo con el contexto. Posteriormente, dos estudios cuantitativos permitieron evaluar las propiedades psicométricas. Participaron 196 y 298 personas respectivamente. La aplicación de la escala se realizó en línea en septiembre de 2020 y abril de 2021. Resultados: la escala incluyó 26 respuestas emocionales asociadas al estrés. En el Análisis Factorial Exploratorio se redujo a nueve emociones negativas (X2=1183, gl=36, p=.001, KMO=.94, 60% de varianza explicada, Alfa ordinal=.93), corroboradas en el Análisis Factorial Confirmatorio (X2=41.87, gl=26, X2/gl=1.61, p=.025; RMR=.036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conclusión: la propuesta exploratoria de la escala para evaluar las respuestas emocionales por el estrés en el traslado presenta valores adecuados para aplicarse en la Zona Metropolitana del Valle de México.

Abstract The stress in urban settings is related to a greater request for personal resources to face situations of daily life, such as the commuting, since in big cities, people spend a lot of time on it, and sometimes is uncomfortable and annoying, which can cause stress. Commuting stress has been assessed, through commuting daily hassles, commuting stressful features and physiological responses, but it is possible assess it through emotional responses. The aim of this study was to develop and assess an exploratory scale of emotional responses for the study of commuting stress by public transport in an urban area of México that is densely populated. Method, a cross sectional design was used, in which a qualitative exploratory study was carried out through 23 individual semi-structured interviews and two focus group, where it was identified the main emotions experienced during the commuting stress to develop the items in the language of the population. Subsequently, those emotions were compared with emotions proposed in previous studies to complement the scale. Thus, 26 emotions were included to assess the commuting stress through emotional responses. Finally, two quantitative studies were carried out to assess the psychometric properties of the scale, in which 196 and 298 people participated, respectively. The scale was applied online in September 2020 and in April 2021. Results, from the 26 emotional stress responses were reduced to nine negative emotions in an Exploratory Factor Analysis (X2=1183, df=36, p=.001, KMO= .94, 60% variance, Alfa ordinal=.93). This solution was corroborated with a Confirmatory Factor Analysis (X2=41.87, d.f.=26, X2/d.f.=1.61, p=.025; RMR= .036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conserve only nine negative emotions is due to statistical analysis but also because some emotions referred to conditions of physical exhaustion or body energy level. On the other hand, positive emotions were related with pleasant commuting situations, not with the commuting stress experience. Conclusion, the exploratory scale to assess the commuting stress through emotional responses presents acceptable values to be applied in this urban area of Mexico.

Evaluación de la capacidad de centrado y transporte apical de los sistemas Reciproc Blue y XP-endo Shaper / Evaluation of the centering and apical transport capacity of Reciproc Blue and XP-endo Shaper systems

Resumen Objetivo: Comparar la capacidad de centrado y el transporte apical de los sistemas Reciproc Blue y XP-endo Shaper en bloques de resina con fotografías pre y posoperatorias yuxtapuestas, mediante un programa de análisis de imágenes. Materiales y Métodos: Se dividieron al azar 20 tacos de resina en dos grupos (n=10) preparados con XP-endo Sha- per y Reciproc Blue respectivamente. Se tomaron fotografías digitales de los tacos, antes y después de la preparación con cada sistema en una misma posición. Luego las fotografías obtenidas fueron yuxtapuestas mediante el software Photo shop. Se midieron las desviaciones del centro del conducto con respecto a la pared interna y externa del mismo en diversos puntos de referencia preestablecidos. Estos datos fueron analizados estadísticamente con el test de ANOVA. Resultados: Ambos sistemas produjeron transporte y desviación respecto a la trayectoria original del conducto radicular, pero el análisis estadístico (ANOVA Factorial 2x8) no cuantificó diferencias significativas entre ambos sistemas (p=0,4044) Conclusiones: Bajo las condiciones de este trabajo, ambos sistemas producen transporte y desviación respecto a la trayectoria original del conducto radicular.

Abstract Aim: To compare the centering capacity and apical transport of the Reciproc Blue and X-Pendo Shaper system in resin blocks with juxtaposed pre and postoperative photographs, using the Photoshop software. Materials and methods: 20 resin plugs were randomly divided into two groups (n=10) that were prepared with XP-endo Shaper and Reciproc Blue respectively. Digital photographs of the blocks were taken, before and after preparation, with each system in the same position. Then the obtained photographs were juxtaposed using Photoshop software. The deviations of the center of the canal, with respect to its inter nal and external wall, were measured at various pre-established reference points. These data were statistically analysed with the ANOVA test. Results: Both systems produced transport and deviation from the original trajectory of the root canal, but the statistical analysis (2x8 Factorial ANOVA) did not quantify significant differences between both systems (p=0.4044) Conclusions: Under the conditions of this work, both systems produce transport and deviation with respect to the original trajectory of the root canal.

Efecto del ácido deoxicólico sobre la regulación del transporte iónico intestinal en la rata / Deoxycholic acid efect on intestinal ionic transport regulation in the rat

The intestine has a very important role in the homeostasis of the internal medium. Bile acids play a regulatory role in the digestion and absorption of nutrients. Among them, deoxycholic acid, when its luminal concentration increases due to bacterial overgrowth, modifies hydroelectrolytic transport, producing an increase in the volume of water and electrolytes in stools.

El intestino tiene un papel muy importante en la homeostasis del medio interno. Los ácidos biliares cumplen una función reguladora en la digestión y absorción de nutrientes. Entre ellos el ácido deoxicólico, cuando aumenta su concentración luminal por sobrecrecimiento bacteriano, modifica el transporte hidroelectrolítico produciendo aumento del volumen de agua y electrolitos en las deposiciones.

Competencies for aeromedical evacuation practices in emergencies and disasters: a scoping review / Competencias para prácticas de evacuación aeromédica en emergencias y desastres: revisión del alcance / Competências para práticas de evacuações aeromédicas em emergências e desastres: revisão de escopo

ABSTRACT Objective: to map the competencies developed in training strategies for air transport practices for patients, in the face of emergency situations and disasters involving chemical, biological, radiological and nuclear (CBRN) agents. Method: this is a scoping review structured in accordance with the JBI and Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews recommendations. The study was carried out in five stages: search for sources in 17 databases, an information portal and two repositories of gray literature, using 125 DeCS, MeSH and Emtree descriptors, without temporal and idiomatic clipping; selection; critical reading of the texts selected by two double-blind reviewers; summary of results and presentation of mapped competencies. Results: a total of 878 studies were analyzed, of which 18 composed the sample. In all, 11 competencies were mapped, with emphasis on the technical training domain. Competencies refer especially to technical-scientific knowledge in disaster situations involving CBRN agents and the safety of patients and professionals involved. Conclusion: the operationalization of artifices to improve qualification processes based on competencies proved to be strategic to increase the quality and safety of patient air transport practices. The approach of the sources on specific aspects of the particularities of practices related to emergencies and disasters involving CBRN agents in training/training processes demonstrates the academic effort to promote the reduction of the risk of these events when, in due course, civil and military institutions and their health operators are activated.

RESUMEN Objetivo: mapear las competencias desarrolladas en estrategias de formación en prácticas de transporte aéreo de pacientes, ante situaciones de emergencia y desastres con agentes químicos, biológicos, radiológicos y nucleares (QBRN). Método: una revisión de alcance estructurada de acuerdo con las recomendaciones del JBI y la lista de verificación Elementos de informe preferidos para revisiones sistemáticas y la extensión Metanalyses para revisiones de alcance. El estudio se realizó en cinco etapas: búsqueda de fuentes en 17 bases de datos, un portal de información y dos repositorios de literatura gris, utilizando 125 descriptores DeCS, MeSH y Emtree, sin recorte temporal e idiomático; selección; lectura crítica de los textos seleccionados por dos revisores doble ciego; resumen de resultados y presentación de competencias mapeadas. Resultados: se analizaron 878 estudios, de los cuales 18 compusieron la muestra. En total, se mapearon 11 competencias, con énfasis en el dominio de formación técnica. Las competencias se refieren especialmente al conocimiento técnico-científico en situaciones de desastres que involucran a agentes QBRN y la seguridad de los pacientes y profesionales involucrados. Conclusión: la operacionalización de artificios para mejorar los procesos de calificación basados ​​en competencias demostró ser estratégica para aumentar la calidad y seguridad de las prácticas de transporte aéreo de pacientes. El abordaje de las fuentes sobre aspectos específicos de las particularidades de las prácticas relacionadas con emergencias y desastres que involucran a agentes QBRN en los procesos de formación/capacitación demuestra el esfuerzo académico por promover la reducción del riesgo de estos eventos cuando, en su momento, se activan las instituciones civiles y militares y sus operadores de salud.

RESUMO Objetivo: mapear as competências desenvolvidas em estratégias de capacitação para práticas de transporte aéreo de pacientes, diante de situações de emergência e desastres envolvendo agentes químicos, biológicos, radiológicos e nucleares (QBRN). Método: revisão de escopo estruturada conforme as recomendações do Joanna Briggs Institute e do checklist Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews. O estudo foi desenvolvido em cinco etapas: busca de fontes em 17 bases de dados, um portal de informação e dois repositórios de literatura cinzenta, utilizando 125 descritores DeCS, MeSH e Emtree, sem recorte temporal e idiomático; seleção; leitura crítica na íntegra dos textos selecionados por dois revisores em duplo cego; síntese dos resultados e apresentação das competências mapeadas. Resultados: foram analisados 878 estudos, dos quais 18 compuseram a amostra. Ao todo, foram mapeadas 11 competências, com destaque para o domínio capacitação técnica. As competências referem-se especialmente ao conhecimento técnico-científico em situações de desastre envolvendo agentes QBRN e à segurança do paciente e dos profissionais envolvidos. Conclusão: a operacionalização de artifícios para aperfeiçoar os processos de capacitação baseados em competências mostrou-se estratégica para elevar a qualidade e a segurança das práticas de transporte aéreo de pacientes. A abordagem das fontes sobre aspectos específicos das particularidades das práticas relacionadas às emergências e desastres envolvendo agentes QBRN em processos de formação/capacitação demonstra o esforço acadêmico de promover a redução do risco desses eventos quando, oportunamente, forem acionadas instituições civis e militares e seus operadores de saúde.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis / Uso de elexacaftor + tezacaftor + ivacaftor em indivíduos com fibrose cística com pelo menos um alelo F508del: revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, −0.16; 95% CI, −0.28 to −0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, −0.03; 95% CI, −0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

RESUMO Objetivo: Avaliar o efeito do tratamento com a combinação de três moduladores da proteína cystic fibrosis transmembrane conductance regulator (CFTR, reguladora de condutância transmembrana em fibrose cística) - elexacaftor + tezacaftor + ivacaftor (ETI) - sobre desfechos clínicos importantes em indivíduos com fibrose cística. Métodos: Revisão sistemática e meta-análise de ensaios clínicos randomizados que compararam o uso de ETI em indivíduos com fibrose cística com pelo menos um alelo F508del com o uso de placebo ou de um comparador ativo como outras combinações de moduladores da CFTR. O estudo foi realizado seguindo as recomendações Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a metodologia Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO). Foram realizadas buscas nos seguintes bancos de dados: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov, desde a sua criação até 26 de dezembro de 2022. O risco de viés foi avaliado por meio da ferramenta de risco de viés da Cochrane, e a qualidade das evidências foi determinada com base no sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: Foram identificados 54 estudos na busca primária. Destes, 6 preencheram os critérios de inclusão e foram analisados (1.127 pacientes: 577 pacientes intervenção e 550 pacientes controle). A meta-análise revelou que o uso de ETI aumentou o VEF1 em porcentagem do previsto [diferença de risco (DR): +10,47%; IC95%: 6,88-14,06], reduziu o número de exacerbações pulmonares agudas (DR: −0,16; IC95%: −0,28 a −0,04) e melhorou a qualidade de vida (DR: +14,93; IC95%: 9,98-19,89) e o IMC (DR: +1,07 kg/m2; IC95%: 0,90-1,25). Os eventos adversos não diferiram entre os grupos (DR: −0,03; IC95%: −0,08 a 0,01), e nenhum dos estudos relatou óbitos. Conclusões: Nossos achados demonstram que o tratamento com ETI melhora substancialmente os desfechos clinicamente significativos centrados no paciente.

Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study / Elexacaftor/tezacaftor/ivacaftor-efetividade clínica e segurança no mundo real. Estudo unicêntrico português

ABSTRACT Objective: To evaluate the effectiveness of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and to characterize its safety profile in cystic fibrosis (CF) patients in a real-world clinical setting. Methods: This was a prospective observational study carried out in a CF referral center in Portugal involving adult CF patients who started treatment with ELX/TEZ/IVA. Clinical characteristics of the patients were collected, and effectiveness and safety data were evaluated. Results: Of the 56 patients followed in the center at the time of the study, 28 were eligible for ELX/TEZ/IVA treatment in accordance with the Portuguese National Authority for Medicines and Health Products at the time of the study. Of these, 24 met the follow-up time requirement to be included in the clinical effectiveness analysis. The mean follow-up time was 167.3 ± 96.4 days. Adverse events were generally mild and self-limited. Significant improvements in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations were observed. No significant differences in outcomes between F508del homozygous and heterozygous patients were found. The effectiveness of this new CFTR modulator combination also applied to patients with advanced lung disease. Conclusions: Treatment with ELX/TEZ/IVA showed effective improvement in real-world clinical practice, namely in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations, with no safety concerns.

RESUMO Objetivo: Avaliar a efetividade do tratamento com elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) e caracterizar seu perfil de segurança em pacientes com fibrose cística (FC) em um cenário clínico de mundo real. Métodos: Estudo observacional prospectivo realizado em um centro de referência em FC de Portugal com pacientes adultos com FC que iniciaram o tratamento com ELX/TEZ/IVA. As características clínicas dos pacientes foram coletadas, e os dados de efetividade e segurança, avaliados. Resultados: Dos 56 pacientes acompanhados no centro na época do estudo, 28 eram elegíveis para o tratamento com ELX/TEZ/IVA de acordo com a Autoridade Nacional do Medicamento e Produtos de Saúde. Destes, 24 atenderam ao requisito de tempo de acompanhamento para inclusão na análise de efetividade clínica. O tempo médio de acompanhamento foi de 167,3 ± 96,4 dias. Os eventos adversos foram geralmente leves e autolimitados. Foram observadas melhoras significativas na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares. Não foram encontradas diferenças significativas nos resultados entre os pacientes homozigotos e heterozigotos para F508del. A efetividade dessa nova combinação de moduladores da CFRT em fibrose cística também se aplica a pacientes com doença pulmonar avançada. Conclusões: O tratamento com ELX/TEZ/IVA demonstrou melhora efetiva na prática clínica real, a saber, na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares, sem preocupações de segurança.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Sexual harassment in public transport among female students at the Federal university of technology Akure, Nigeria

Background: Every day females experience different types of sexual harassment while using public transportation worldwide. Objective: This study aims to determine the prevalence of sexual harassment amongst female students who travel by public transportation at the Federal University of Technology Akure (FUTA) Nigeria. Materials and Methods: A cross-sectional descriptive study. Data was collected using electronic questionnaires and analyzed with IBM SPSS Statistics version 21. Frequencies and percentages were used for data summary. Association between variables was determined using Chi Square test. Statistical significance was a p-value < 0.05. Results: Ninety-three percent of female students in FUTA had experienced sexual harassment. Among those who had experienced sexual harassment, 98.4% were single, 81.5% lived off campus, 79.0% used public bus, 45.4% commuted daily, 84.7% was in an overcrowded vehicle and 52.9% was in the evening. There was a significant association between sexual harassment and marital status (p = 0.033), place of residence (p = 0.019), mode of public transportation (p = 0.014), time of travel (p = 0.018). Verbal sexual harassment was most prevalent (91.1%), followed by physical sexual harassment (87.6%) and non-verbal sexual harassment (82%). Conclusion: This study found a high prevalence of sexual harassment among female university students in FUTA using public transportation, which occurs in a variety of scenarios, particularly in crowded vehicles during rush hour

Mechanism of gigantol in transmembrane transport in human lens epithelial cells / 中国中药杂志

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

Buyang Huanwutang Treats Diabetic Peripheral Neuropathy via Mitochondrial Transport in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） via mitochondrial transport. MethodDiabetes in SD rats was induced by a high-carbohydrate/high-fat diet and intraperitoneal injection of streptozotocin （STZ）. The 45 diabetic rats were randomly assigned into a DPN group， an alpha-lipoic acid （60 mg·kg-1·d-1） group， and a Buyang Huanwutang （15 g·kg-1·d-1） group， with 15 rats in each group. Fifteen normal SD rats were fed with the standard diet and set as the control group. The rats were administrated with corresponding drugs by gavage for 12 weeks. The paw withdraw threshold （PWT） and motor nerve conduction velocity （MNCV） were measured at the end of medication， and the sciatic nerve and the bilateral dorsal root ganglia of L4-5 were collected. The injury model of NSC34 cells was established by treating with 50 mmol·L-1 glucose and 250 μmol·L-1 sodium palmitate. The NSC34 cells were then randomly assigned into a blank （10% blank serum） group， a DPN （10% blank serum） group， an apha-lipoic acid （10% apha-lipoic acid-containing serum） group， a Buyang Huanwutang （10% Buyang Huanwutang-containing serum） group， and a Buyang Huanwutang + Compound C （CC） （10% Buyang Huanwutang-containing serum + 10 μmol·L-1 CC） group. The cell intervention lasted for 24 h. The immunofluorescence method， immunohistochemistry， and Western blot were employed to determine the expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， phosphorylated cAMP-response element binding protein （p-CREB）， kinesin family member 5A （KIF5A）， and dynein cytoplasmic 1 intermediate chain 2 （DYNC1I2）. ResultCompared with the control group， the DPN group of rats showed increased fasting blood glucose （P<0.01）， decreased MNCV and PWT （P<0.01）， down-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01）， and up-regulated expression of DYNC1I2 （P<0.01）. Compared with the DPN group， drug intervention groups showed increased MNCV and PWT （P<0.01）， up-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01）， and down-regulated expression of DYNC1I2 （P<0.05， P<0.01）. The Buyang Huanwutang group had higher levels of MNCV and KIF5A （P<0.05） and lower level of DYNC1I2 （P<0.01） than the apha-lipoic acid group. Compared with the blank group， the DPN group of NSC34 cells showed decreased levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） and increased level of DYNC1I2 （P<0.01）. The apha-lipoic acid group and Buyang Huanwutang group had higher levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01） and lower level of DYNC1I2 （P<0.01） in NSC34 cells than the DPN group. Buyang Huanwutang group had higher KIF5A level （P<0.05） in NSC34 cells than the apha-lipoic acid group. Moreover， the Buyang Huanwutang + CC group had lower levels of KIF5A， DYNC1I2， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） in NSC34 cells than the Buyang Huanwutang group. ConclusionBuyang Huanwutang may regulate mitochondrial anterograde transport via the AMPK/CREB pathway to prevent and treat DPN.

Application of transport ventilator in the inter-hospital transport of critically ill children / 中国当代儿科杂志

OBJECTIVES@#To study the application value of transport ventilator in the inter-hospital transport of critically ill children.@*METHODS@#The critically ill children in Hunan Children's Hospital who were transported with or without a transport ventilator were included as the observation group (from January 2019 to January 2020; n=122) and the control group (from January 2018 to January 2019; n=120), respectively. The two groups were compared in terms of general data, the changes in heart rate, respiratory rate, and blood oxygen saturation during transport, the incidence rates of adverse events, and outcomes.@*RESULTS@#There were no significant differences between the two groups in sex, age, oxygenation index, pediatric critical illness score, course of disease, primary disease, heart rate, respiratory rate, and transcutaneous oxygen saturation before transport (P>0.05). During transport, there were no significant differences between the two groups in the changes in heart rate, respiratory rate, and transcutaneous oxygen saturation (P>0.05). The incidence rates of tracheal catheter detachment, indwelling needle detachment, and sudden cardiac arrest in the observation group were lower than those in the control group during transport, but the difference was not statistically significant (P>0.05). Compared with the control group, the observation group had significantly shorter duration of mechanical ventilation and length of stay in the pediatric intensive care unit and significantly higher transport success rate and cure/improvement rate (P<0.05).@*CONCLUSIONS@#The application of transport ventilator in the inter-hospital transport can improve the success rate of inter-hospital transport and the prognosis in critically ill children, and therefore, it holds promise for clinical application in the inter-hospital transport of critically ill children.

Hemilateral bone longitudinal transport technique for the treatment of hemilateral defects of long bones of lower limbs / 中国骨伤

OBJECTIVE@#To explore clinical efficacy of Ilizarov hemilateral bone longitudinal transport technique in treating hemilateral bone defects associated with chronic osteomyelitis of lower extremity long bones.@*METHODS@#Clinical data of 13 patients with hemilateral bone defects caused by chronic osteomyelitis of lower extremity long bones and treated by Ilizarov hemilateral bone longitudinal transport technique were retrospective analyzed, including 10 males and 3 female, aged from 14 to 55 years old;4 patients occurred femoral and 9 patients occurred tibial;10 patients were diagnosed as traumatic osteomyelitis and 3 patients as hematogenous osteomyelitis. The anatomical classification of Cierny-Mader in 13 patients was type Ⅲ. Bone and wound healing, postopertaive complication, and bony and functional results were observed by Paley evaluation standard.@*RESULTS@#After removing external fixator, all patients were followed up from 6 to 70 months. Transporting time ranged from 54 to 158 d. And the time in external fixation ranged from 6.8 to 19.5 months. External fixation index (EFI) ranged from 1.23 to 1.6 months/cm. According to Paley's evaluation criteria, bony results were excellent in 13 patients;functional results showed excellent in 12 patients and good in 1 patient. Two patients occurred poor union on the docking sites and healed with autogenous iliac bone graft. The callus at the extended area was poorly mineralized and improved significantly when treated with low-intensity pulsed ultrasound in one patient. All patients had good wound healing without recurrence of osteomyelitis and refracture. There was no vascular and nerve injury and axial deviation in all patients and they were satisfied with the appearance and function of lower limbs. The range of motion of knee and ankle joint before operation was 120 ° to 150 ° and 35 °to 80 ° respectively, and at the latest follow-up was 110 ° to 140 ° and 30 ° to 75 ° .@*CONCLUSION@#Ilizarov hemilateral bone longitudinal transport technique is effective in treating infective hemilateral bone defects of lower extremity long bones, which could not only simplify architecture of external fixation, but also reduce the number of fixation pins, shorten the time in external fixator and decrease the incidence of pin tract infection. However, this technique is highly demanding, and the growth of callus in extended region and healing of bone apposition should be noticed.

Effectiveness of tibial transverse transport combined with modified neurolysis in treatment of diabetic foot ulcers / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of tibial transverse transport (TTT) combined with modified neurolysis in treatment of diabetic foot ulcer (DFU) through a prospective randomized controlled study.@*METHODS@#The patients with DFU and diabetic peripheral neuropathy, who were admitted between February 2020 and February 2022, were selected as the research objects, of which 31 cases met the selection criteria and were included in the study. The patients were divided into two groups by random number table method. The 15 patients in the trial group were treated with TTT combined with modified neurolysis, and the 16 patients in the control group received treatment with TTT alone. There was no significant difference in gender, age, duration of DFU, ulcer area, Wagner classification, as well as preoperative foot skin temperature, visual analogue scale (VAS) score, ankle-brachial index (ABI), motor nerve conduction velocity (MNCV) of the common peroneal nerve, MNCV of the tibial nerve, MNCV of the deep peroneal nerve, two-point discrimination (2-PD) of heel, and cross-sectional area (CSA) of the common peroneal nerve between the two groups ( P>0.05). The time for ulcer healing, foot skin temperature, VAS scores, ABI, 2-PD of heel, and CSA of the common peroneal nerve before operation and at 6 and 12 months after operation were recorded and compared between groups. The differences in MNCV of the common peroneal nerve, MNCV of the tibial nerve, and MNCV of the deep peroneal nerve between pre-operation and 12 months after operation were calculated.@*RESULTS@#All patients in both groups were followed up 12-24 months (mean, 13.9 months). The surgical incisions in both groups healed by first intention and no needle tract infections occurred during the bone transport phase. Ulcer wounds in both groups healed successfully, and there was no significant difference in the healing time ( P>0.05). During the follow-up, there was no ulcer recurrences. At 12 months after operation, the MNCV of the common peroneal nerve, the MNCV of the tibial nerve, and the MNCV of the deep peroneal nerve in both groups accelerated when compared to preoperative values ( P<0.05). Furthermore, the trial group exhibited a greater acceleration in MNCV compared to the control group, and the difference was significant ( P<0.05). The foot skin temperature, VAS score, ABI, 2-PD of heel, and CSA of the common peroneal nerve at 6 and 12 months after operation significantly improved when compared with those before operation in both groups ( P<0.05). The 2-PD gradually improved over time, showing significant difference ( P<0.05). The 2-PD of heel and VAS score of the trial group were superior to the control group, and the differences were significant ( P<0.05). There was no significant difference in ABI, foot skin temperature, and CSA of the common peroneal nerve between groups after operation ( P>0.05).@*CONCLUSION@#Compared with TTT alone, the TTT combined with modified neurolysis for DFU can simultaneously solve both microcirculatory disorders and nerve compression, improve the quality of nerve function recovery, and enhance the patient's quality of life.

The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

Proteomic Study on the Effect of Wenshen Tongdu Formula （温肾通督方） on Spleen B Cells in Spinal Cord Injury Model Mice / 中医杂志

ObjectiveTo explore the effects and possible mechanism of Wenshen Tongdu Formula （温肾通督方， WTF） on spinal cord injury. MethodsThirty-six C57BL/6 female mice were randomly divided into sham operation group， model group and WTF group， with 12 mice in each group. The spinal cord injury model was established in the model group and the WTF group using the modified Allen's method， while in the sham operation group the spinal cord was only exposed. Since the 1st day after surgery， 50 g/（kg·d） of WTF solution was given to the WTF group by gavage， while 20 ml/（kg·d） of normal saline was given to the sham operation and model group by gavage， all for 14 days. Before surgery and on the 1st， 7th， and 14th days after surgery， the motor function of the mice was evaluated using the inclined plane test and hind limb motor function score （by BMS）. On the 3rd day after surgery， the nerve electrophy-siology was detected through electromyography and motor evoked potential； the spleen length was measured， and B cells in the spleen were sorted by magnetic beads； the differential expression of proteins were detected through proteomics technology； and the protein expression of mitochondrial outer membrane transport porin 20 （Tom20） and downstream cleaved caspase-3 in spleen B cells were measured using Western blotting. On the 14th day after surgery， MRI was used to observe the recovery of the spinal cord. ResultsCompared to those in the sham operation group at the same time， the BMS scores and subscores and the inclined plane test angle in the model group were reduced on the 1st， 7th and 14th days after surgery； the peak value of electromyogram and motor evoked potential were reduced， and the spleen length was shortened， while the expression of Tom20 and cleaved caspase-3 increased in splenic B cells increased （P＜0.05）. Compared to those in the model group at the same time， the BMS subscores on the 14th day and the angle of the inclined plane test on the 7th and 14th days after surgery increased in the WTF group； the peak value of electromyography and motor evoked potential， as well as the length of spleen increased， and the expression of Tom20 and cleaved caspase-3 decreased （P＜0.05）. The proteomics results showed that there were 100 differential proteins in the WTF group versus the model group， of which 37 were up-regulated and 63 were down-regulated. GO enrichment analysis showed that differential proteins mainly played their roles in oxygen binding， exogenous apoptosis negative feedback， zinc ion response， and oxygen transport. KEGG enrichment analysis showed that differential proteins were mainly concentrated in metabolic pathways， Huntington's disease， oxidative phosphorylation and other pathways. Subcellular localization showed that differential proteins were associated with mitochondria. Magnetic resonance imaging on the 14th day after surgery showed that the spinal cord structure of the mice in the sham operation group was intact， and the segments were clear， with normal spinal cord signal； the low signal area in the spinal cord injury area increased in the model group， and the spinal cord became significantly thinner； the injured segment had obvious depression in the WTF group， but the structure was more complete than that in the model group. ConclusionWTF may promote spinal cord injury repair by regulating immune function， and its mechanism may be related to inhibiting pyroptosis of spleen B cells.