Phospholipase D regulates ferroptosis signal transduction in mouse spleen hypoxia response

High-altitude hypoxia exposure can lead to phospholipase D-mediated lipid metabolism disorder in spleen tissues and induce ferroptosis. Nonetheless, the key genes underlying hypoxia-induced splenic phospholipase D and the ferroptosis pathway remain unclear. This study aimed to establish a hypoxia animal model. Combined transcriptomic and proteomic analyses showed that 95 predicted target genes (proteins) were significantly differentially expressed under hypoxic conditions. Key genes in phospholipase D and ferroptosis pathways under hypoxic exposure were identified by combining Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis techniques. Gene set enrichment analysis (GSEA) showed that the differential gene sets of the phospholipase D and ferroptosis signaling pathways were upregulated in the high-altitude hypoxia group. The genes in the phospholipase D signalling pathway were verified, and the expression levels of KIT and DGKG were upregulated in spleen tissues under hypoxic exposure. Subsequently, the mRNA and protein expression levels of genes from the exogenous pathway such as TFRC, SLC40A1, SLC7A11, TRP53, and FTH1 and those from the endogenous pathway such as GPX4, HMOX1, and ALOX15 differentials in the ferroptosis signalling pathway were verified, and the results indicated significant differential expression. In summary, exposure to high-altitude hypoxia mediated phospholipid metabolism disturbance through the phospholipase D signalling pathway and further induced ferroptosis, leading to splenic injury.

Influencia de la NeuroEPO en el corazón fetal en un modelo de insuficiencia placentaria en ratas

Fundamento: la insuficiencia placentaria es la causa más común del retardo del crecimiento intrauterino, que puede provocar alteraciones cardiovasculares. Recientemente, se han desarrollado terapias con eritropoyetina que protegen los tejidos cardiacos con hipoxia. Objetivo: evaluar la influencia de la eritropoyetina recombinante humana con bajo contenido de ácido siálico (NeuroEPO) en el corazón fetal en un modelo de insuficiencia placentaria en ratas. Métodos: se utilizaron 14 ratas Wistar gestadas con ligadura unilateral de la arteria uterina derecha en el día 16 de la gestación. Ese mismo día, a siete ratas se le administró NeuroEPO (0,5 mg/kg/día subcutáneo por tres días) y al resto placebo. En el día 20 de la gestación los fetos se dividieron en cuatro grupos: un grupo control, un grupo con retardo del crecimiento intrauterino, un grupo control NeuroEPO y un grupo con retardo del crecimiento intrauterino y NeuroEPO. En los fetos se obtuvo el peso placentario, peso fetal y la eficacia placentaria. En el estudio histológico se cuantificó el número de cardiomiocitos, número de vasos sanguíneos y cantidad de las fibras de colágenos. Resultados: el grupo con retardo del crecimiento intrauterino presentó una disminución del peso fetal, del número de cardiomiocitos, del número de vasos sanguíneos y un aumento en la cantidad de fibras colágenas (p<0.05). Al tratar con NeuroEPO a los fetos con retardo en el crecimiento intrauterino, aumentó el peso fetal, aunque el peso no fue similar al control. El resto de las variables se comportaron semejantes al control. Conclusiones: la administración de esta molécula mejoró el peso fetal y permitió un equilibrio adecuado en el desarrollo del corazón fetal, quizás, debido a los efectos citoprotectores de esta molécula.

Foundation: placental insufficiency is the most common cause of intrauterine growth retardation, which can cause cardiovascular alterations. Recently, erythropoietin therapies have been developed that protect hypoxic cardiac tissues. Objective: To evaluate the influence of human recombinant erythropoietin with low sialic acid content (NeuroEPO) on the fetal heart in a rat model of placental insufficiency. Methods: 14 Wistar rats gestated with unilateral ligation of the right uterine artery on day 16 of gestation were used. That same day, seven rats were administered NeuroEPO (0.5 mg/kg/day subcutaneously for three days) and the rest received placebo. On day 20 of gestation, the fetuses were divided into four groups: a control group, a group with intrauterine growth retardation, a NeuroEPO control group, and a group with intrauterine growth retardation and NeuroEPO. In the fetuses, placental weight, fetal weight and placental efficiency were obtained. In the histological study, the number of cardiomyocytes, number of blood vessels and quantity of collagen fibers were quantified. Results: the group with intrauterine growth retardation presented a decrease in fetal weight, the number of cardiomyocytes, the number of blood vessels and an increase in the amount of collagen fibers (p<0.05). When fetuses with intrauterine growth retardation were treated with NeuroEPO, fetal weight increased, although the weight was not similar to the control. The rest of the variables behaved similar to the control. Conclusions: the administration of this molecule improved fetal weight and allowed an adequate balance in the development of the fetal heart, perhaps due to the cytoprotective effects of this molecule.

Síndrome de hipoventilación del obeso. Presentación de un caso

La obesidad se ha convertido en una importante causa de comorbilidades, por lo cual es importante reconocer de forma temprana las enfermedades asociadas a esta afección, así como su tratamiento. El síndrome de hipoventilación del obeso o también llamado síndrome de Pickwick se ha definido por la triada de obesidad, hipoventilación diurna y respiración alterada durante el sueño, en ausencia de otra enfermedad que explique las alteraciones respiratorias. Se presenta el caso de un paciente de 53 años de edad, de color de piel blanca, masculino, de procedencia urbana, con antecedentes patológicos personales de hipertensión arterial, artritis gotosa, obesidad mórbida, angina de pecho inestable, episodios previos de fibrilación auricular y síndrome de Pickwick sin tratamiento para ello. El día 12 de febrero del 2023 fue traído por sus familiares al Hospital Dr. Gustavo Aldereguía Lima de la provincia Cienfuegos, por presentar, desde hacía siete días atrás, dificultad para respirar, fiebre de 39 ºC, y el día anterior había comenzado a expectorar con sangre. Se describen los procedimientos realizados y tratamientos ante cada complicación, hasta su fallecimiento. Por la importancia que tiene el diagnóstico, control y seguimiento a estos pacientes obesos con comorbilidades, para evitar desenlaces fatales, se decidió la presentación del caso.

Obesity has become an important cause of comorbidities, it is important to recognize the diseases associated with this condition early, as well as its treatment. Obese hypoventilation syndrome, also called Pickwick syndrome, has been defined by the triad of obesity, daytime hypoventilation and altered breathing during sleep, in the absence of another disease that explains the respiratory alterations. The case of a 53-years-old patient, white skin color, male, from urban origin, with a personal pathological history of high blood pressure, gouty arthritis, morbid obesity, unstable angina pectoris, previous episodes of atrial fibrillation and Pickwick syndrome without treatment for it, it is presented. On February the 12th, 2023, he was brought by his family to the Dr. Gustavo Aldereguía Lima Hospital in the Cienfuegos province, because he had had difficulty breathing, a fever of 39ºC, for seven days, and the day before he had begun to expectorate blood. The performed procedures and treatments for each complication are described, until his death. Due to the importance of diagnosis, control and follow-up of these obese patients with comorbidities, to avoid fatal outcomes, it was decided to present the case.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Acute physiological responses to "recovery intermittent hypoxia" in hiit / Respuestas agudas a la "hipoxia intermitente de recuperación" en el hiit / Respostas fisiológicas agudas à "hipóxia intermitente de recuperação" no hiit

ABSTRACT Introduction: Traditional intermittent hypoxia training improves sport performance after short periods of exposure, but acute exposure to intermittent hypoxia leads to decreased training intensity and technical quality. The solution to overcome these negative effects may be to perform efforts in normoxia and the intervals between efforts in hypoxia, maintaining the quality of training and the benefits of hypoxia. Objective: This study aimed to evaluate the acute physiological responses to hypoxia exposure during recovery between high intensity efforts. Materials and methods: Randomized, one-blind, placebo-controlled study. Sixteen men performed a graded exercise test to determine their maximal intensity and two sessions of high-intensity interval training. The training intervals could be in hypoxia (HRT), FIO2: 0.136 or normoxia (NRT), FIO2: 0.209. During the two-minute interval between the ten one-minute efforts, peripheral oxygen saturation (SpO2), heart rate (HR), blood lactate ([La]), blood glucose ([Glu]) were constantly measured. Results: There were differences in HR (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p < 0.01) and SpO2 (TRN = 96.9 ± 1.0%; TRH = 86.2 ± 3.5%, p < 0.01). No differences in [La] and [Glu] TRN (4.4 ± 1.7 mmol.l-1; 3.9 ± 0.5 mmol.l-1) and TRH (5.2 ± 2.0 mmol.l-1; 4.0 ± 0.8 mmol.l-1, p = 0.17). Conclusion: The possibility of including hypoxia only in the recovery intervals as an additional stimulus to the training, without decreasing the quality of the training, was evidenced. Level of Evidence II; Randomized Clinical Trial of Minor Quality.

RESUMEN Introducción: El entrenamiento tradicional en hipoxia intermitente mejora el rendimiento deportivo tras cortos periodos de exposición, sin embargo, la exposición aguda a la hipoxia intermitente conduce a una disminución de la intensidad del entrenamiento y de la calidad técnica. La solución para superar estos efectos negativos puede ser realizar los esfuerzos en normoxia y los intervalos entre esfuerzos en hipoxia, manteniendo la calidad del entrenamiento y los beneficios de la hipoxia. Objetivo: Este estudio pretendía evaluar las respuestas fisiológicas agudas a la exposición a la hipoxia durante la recuperación entre esfuerzos de alta intensidad. Materiales y métodos: Estudio aleatorizado, a ciegas y controlado con placebo. Dieciséis hombres realizaron una prueba de ejercicio graduado para determinar su intensidad máxima y dos sesiones de entrenamiento por intervalos de alta intensidad. Los intervalos de entrenamiento podían ser en hipoxia (HRT), FIO2: 0,136 o normoxia (NRT), FIO2: 0,209. Durante el intervalo de dos minutos entre los diez esfuerzos de un minuto, se midieron constantemente la saturación periférica de oxígeno (SpO2), la frecuencia cardiaca (FC), el lactato en sangre ([La]) y la glucemia ([Glu]). Resultados: Hubo diferencias en la FC (TRN = 120 ± 14 lpm; TRH = 129 ± 13 lpm, p < 0,01) y la SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p < 0,01). No hubo diferencias en [La] y [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) y TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusión: Se evidenció la posibilidad de incluir hipoxia sólo en los intervalos de recuperación como estímulo adicional al entrenamiento sin disminuir la calidad del mismo. Nivel de Evidencia II; Ensayo Clínico Aleatorizado de Baja Calidad.

RESUMO Introdução: O treinamento de hipóxia intermitente tradicional melhora o desempenho esportivo após curtos períodos de exposição, porém a exposição aguda à hipóxia intermitente leva à diminuição da intensidade do treinamento e da qualidade técnica. A solução para superar esses efeitos negativos pode ser realizar esforços em normóxia e os intervalos entre os esforços em hipóxia, mantendo a qualidade do treinamento e os benefícios da hipóxia. Objetivo: Este estudo teve como objetivo avaliar as respostas fisiológicas agudas à exposição de hipóxia durante a recuperação entre esforços de alta intensidade. Materiais e métodos: Estudo aleatório e one-blinded, com efeito placebo controlado. Dezesseis homens realizaram um teste de exercício graduado para determinar sua intensidade máxima e duas sessões de treinamento intervalado de alta intensidade. Os intervalos de treinamento podem ser em hipóxia (TRH), FIO2: 0,136 ou normóxia (TRN), FIO2: 0,209. Durante os dois minutos de intervalo entre os dez esforços de um minuto, foram medidos constantemente a saturação periférica de oxigênio (SpO2), frequência cardíaca (FC), lactato sanguíneo ([La]), glicemia ([Glu]). Resultados: Houve diferenças na FC (TRN = 120 ± 14 bpm; TRH = 129 ± 13 bpm, p <0,01) e SpO2 (TRN = 96,9 ± 1,0%; TRH = 86,2 ± 3,5%, p <0,01). Sem diferenças em [La] e [Glu] TRN (4,4 ± 1,7 mmol.l-1; 3,9 ± 0,5 mmol.l-1) e TRH (5,2 ± 2,0 mmol.l-1; 4,0 ± 0,8 mmol.l-1, p = 0,17). Conclusão: Evidenciou-se a possibilidade de incluir a hipóxia apenas nos intervalos de recuperação como um estímulo adicional ao treinamento, sem diminuir a qualidade do treinamento. Nível de Evidência II; Estudo Clínico Randomizado de Menor Qualidade.

Cobalt Chloride as a Hypoxia Mimicking Agent Induced HIF-1α and mTOR Expressions of Human Umbilical Cord Mesenchymal Stem Cells

ABSTRACT Objective: To assess the effects of cobalt chloride (CoCl2) as a hypoxia mimicking agent on human umbilical cord mesenchymal stem cells (hUCMSCs) expression of HIF-1α and mTOR for use in regenerative dentistry. Material and Methods: Human umbilical cord mesenchymal stem cells were isolated and then cultured. The characteristics of stemness were screened and confirmed by flow cytometry. The experiment was conducted on hypoxia (H) and normoxia (N) groups. Each group was divided and incubated into 24-, 48-, and 72-hours observations. Hypoxic treatment was performed using 100 µM CoCl2 on 5th passage cells in a conventional incubator (37°C; 5CO2). Then, immunofluorescence of HIF-1α and mTOR was done. Data was analyzed statistically using One-way ANOVA and Tukey's HSD. Results: Significant differences were found between normoxic and hypoxic groups on HIF-1α (p=0.015) and mTOR (p=0.000) expressions. The highest HIF-1α expression was found at 48 hours in the hypoxia group, while for mTOR at 24 hours in the hypoxia group. Conclusion: Hypoxia using cobalt chloride was able to increase human umbilical cord mesenchymal stem cells expression of HIF-1α and mTOR.

Escenarios para el diagnóstico de encefalopatía hipóxico isquémica e inicio de tratamiento con hipotermia controlada en recién nacidos con asfixia perinatal

La hipoxia isquemia perinatal y su complicación más temida, la encefalopatía hipóxica isquémica, continúa siendo uno de los principales motivos de ingreso a las unidades de cuidados neonatales. En la actualidad la hipotermia controlada es el tratamiento recomendado para los pacientes con encefalopatía moderada a severa, dado su carácter de neuroprotección ante la injuria cerebral hipóxico isquémica. Si bien los criterios de inclusión en esta terapia han sido bien establecidos, aún hay dificultades tanto en la identificación precoz de aquellos que pueden verse beneficiados, como en la toma de decisiones ante situaciones de controversia entre la evidencia disponible y la que se está gestando en estudios en curso. Este artículo pretende aportar herramientas al clínico para abordar diferentes escenarios que surgen de la práctica diaria.

Summary: Perinatal hypoxic ischemia and its most feared complication, hypoxic ischemic encephalopathy, remain one of the main reasons for admission to neonatal care. Controlled hypothermia is currently the recommended treatment for patients with moderate to severe encephalopathy, given its neuroprotective nature against hypoxic-ischemic brain injury. Although the inclusion criteria for this therapy have been well established, there are still difficulties both in the early identification of those who may benefit, and in making decisions regarding situations of controversy between the available evidence and that being developing in ongoing studies. This paper aims at providing tools so that clinicians can address different scenarios that arise during their daily practice.

A hipóxia isquêmica perinatal e sua complicação mais temida, a encefalopatia hipóxico-isquêmica, continuam sendo um dos principais motivos de internação em unidades de cuidados neonatais. A hipotermia controlada é atualmente o tratamento recomendado para pacientes com encefalopatia moderada a grave, dada a sua natureza neuroprotetora contra lesão cerebral hipóxico-isquêmica. Embora os critérios de inclusão dessa terapia estejam bem estabelecidos, ainda há dificuldades tanto na identificação precoce daqueles que podem se beneficiar, quanto na tomada de decisões em situações de controvérsia entre as evidências disponíveis e aquelas que estão se desenvolvendo em estudos em andamento. Este paper tem como objetivo fornecer ferramentas aos clínicos para abordar diferentes cenários que surgem da prática diária.

Comparison of HIF-1α and survivin levels in patients with diabetes and retinopathy of varying severity

ABSTRACT Purpose: This study measured serum hypoxia--inducible factor-1 (HIF-1α) and survivin levels in patients with diabetes and investigated their association with the severity of retinopathy. Methods: This study included 88 patients with type 2 diabetes mellitus who underwent routine eye examinations. Three groups were created. Group 1 consisted of patients without diabetic retinopathy. Group 2 included patients with non-proliferative diabetic retinopathy. Group 3 included patients with proliferative diabetic retinopathy. To measure serum HIF-1α and survivin levels, venous blood samples were collected from patients. Results: The mean HIF-1α levels in groups 1, 2, and 3 were 17.30 ± 2.19, 17.79 ± 2.34, and 14.19 ± 2.94 pg/ml, respectively. Significant differences were detected between groups 1 and 3 (p=0.01) and between groups 2 and 3 (p=0.01). The mean survivin levels in groups 1, 2, and 3 were 42.65 ± 5.37, 54.92 ± 5.55, and 37.46 ± 8.09 pg/ml, respectively. A significant difference was only detected between groups 2 and 3 (p=0.002). Conclusion: The present study revealed that serum HIF-1α and survivin levels are increased in patients with non-proliferative diabetic retinopathy compared to those in patients without diabetic retinopathy.

Platypnea-orthodeoxia syndrome: an intriguing perioperative hypoxemia case report

Abstract Platypnea-orthodeoxia syndrome (POS) is a rare condition of positional hypoxemia and dyspnea. The following is a case of hypoxemia for no obvious reason in the perioperative scenario. A 70-year-old male patient was submitted to a radical prostatectomy. On several occasions after anesthetic induction, peripheral oxygen saturation decreased without any understandable cause. In the postanesthesia care unit, severe hypoxemia occurred in the upright position, oddly correcting with recumbency. An echocardiography showed a right-to-left intracardiac shunt through a patent foramen ovale with no pulmonary hypertension, establishing POS. Achieving this diagnosis required a broad workup with a high degree of suspicion.

Methylene blue as an adjuvant during cardiopulmonary resuscitation: an experimental study in rats

Abstract Introduction: Methylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. Method: Thirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11 /group) and treated with EPI 20 μg.kg−1 (EPI), EPI 20 μg.kg−1 + MB 2 mg.kg−1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. Results: No differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI +MB: 43.7 [116.31] ng/mL, p < 0.05). Conclusion: The coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

Single-Lung Ventilation in Infants for Surgical Repair of Coarctation of The Aorta Without Cardiopulmonary Bypass

ABSTRACT Objective: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB). Methods: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R). Results: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05). Conclusion: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.

Effects of hypoxia-inducible factors on tumor mesenchymal cells: a review / 预防医学

@#Hypoxia is the most common tumor microenvironment caused by rapid proliferation of tumor cells, and hypoxia-inducible factor (HIF) is the main transcription factor for tumor cells to adapt to hypoxia. Current research has found that HIF can interact with a variety of mesenchymal cells such as fibroblasts, endothelial cells and immune cells in the tumor microenvironment, leading to the transcription and expression of target genes in response to hypoxia, which ultimately promotes tumor angiogenesis, and induces physiological changes such as migration, invasion, and immune escape of tumor cells. However, the signaling pathways involved in the HIF regulatory mechanism are complex, and the mechanism of HIF in the tumor microenvironment need to be further investigated, also most HIF inhibitors are still in the preclinical research stage. This paper reviews the research progress on the effects of HIF on tumor mesenchymal stromal cells to provide a theoretical basis for the diagnosis, prevention and treatment of tumors targeting HIF.

Characterization of group Ⅰ metabotropic glutamate receptors in rat superior cervical ganglion and their changes following chronic intermittent hypoxia / 解剖学报

Objective To observe the expression and localization of group Ⅰ metabotropic glutamate receptors (mGluR1/ 5) in rat superior cervical ganglion (SCG) and the effect of chronic intermittent hypoxia (CIH) on mGluR1/ 5 protein level. Methods Twelve male SD rats were randomly divided into control group(Ctrl)and CIH group(CIH), 6 rats in each group. After 6 weeks of modeling, the effect of CIH on mGluR1/ 5 protein level was detected by Western blotting, the expression and distribution of mGluR1/ 5 in SCG were detected by immunohistochemistry and double-immunofluorescent staining. Results mGluR1/ 5 was expressed in rat SCG. mGluR1 was distributed in neurons and small intensely fluorescent (SIF) cells, but not in satellite glial cells (SGCs), nerve fibers and blood vessels, whereas mGluR5 was mainly distributed in nerve fibers and a little in neurons, but not in SGCs, SIF cells and blood vessels. CIH increased the protein levels of mGluR1/ 5 (P<0. 01) in rat SCG. Conclusion Both mGluR1 and mGluR5 are expressed in the rat SCG, but their distribution are different, and the increased protein levels of both may be involved in CIH-induced hypertension.

Effect of exogenous hydrogen sulfide on hypoxia/reoxygenation injury in glomerular mesangial cells and its mechanism / 中国药理学通报

Aim To explore the effect of exogenous hydrogen sulfide ( H2 S ) on hypoxia/reoxygenation ( H/R) injury in glomerular mesangial cells and elucidate its relevant mechanism. Methods H/R induced mouse mesangial cell line ( SV40MES13 ) to establish cell damage model. Cell viability was detected by cell proliferation kit ( CCK8 ), the content of H

Effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension in mice and its mechanism / 中国药理学通报

Aim To study the effect of menthol on hypobaric hypoxia-induced pulmonary arterial hypertension and explore the underlying mechanism in mice. Methods 10 to 12 weeks old wild type (WT) mice and TRPM8 gene knockout (TRPM8

Correlation Between Expression of HIF-1α and Prognosis of Arsenic-containing Chinese Herbal Compound in Treatment of Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

Inhibition of Pannus Formation by Wutoutang in AIA Rats with Wind-cold-dampness Bi Syndrome Via Down-regulating HIF-1α/VEGFA/Ang Signaling Pathway / 中国实验方剂学杂志

ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg-1·d-1）， and indometacin group （10 mg·kg-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

Effects of plateau environment on tear indexes and related anatomical structures of rabbits / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P&#x003C;0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.

Mechanism of Shugan Huazheng Prescription Against Liver Fibrosis Based on HIF-1α/VEGF/TGF-β1 Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Shugan Huazheng prescription on hepatic fibrosis model rats induced by carbon tetrachloride （CCl4） and explore whether it plays its role through hypoxia-induced factor-1α/vascular endothelial growth factor/transforming growth factor-β1 （HIF-1α/VEGF/TGF-β1） pathway. MethodA total of 54 male SPF SD rats were randomly divided into six groups： blank group， model group， colchicine group （0.2 mg·kg-1）， and high-， medium-， and low-dose groups （29.52， 14.76， and 7.38 g·kg-1） of Shugan Huazheng prescription， with nine rats in each group. The molding was conducted three times a week for eight weeks. Administration began the day after the first injection， and the drug intervention was once a day for eight weeks. On the day after the last administration， the rats were deprived of food and water， and they were killed the next day， during which the physiological status of each group of rats was dynamically monitored. The pathological changes in the liver were observed by hematoxylin-eosin （HE） staining， and the content of hydroxyproline （HYP） and angiotensin Ⅱ （AngⅡ） in liver tissue were detected by enzyme-related immunosorbent assay （ELISA）. Real-time fluorescent quantitative PCR （Real-time PCR） was used to determine the mRNA expression levels of HIF-1α， VEGF， and TGF-β1 in liver tissue， and immunohistochemical method （IHC） and Western blot were used to detect the protein expression levels of HIF-1α， VEGF， and TGF-β1 in liver tissue. ResultCompared with the blank group， the overall condition of rats in the model group decreased significantly. The proliferation of connective tissue and the increase in adipose cells between hepatocytes were obvious. The content of HYP and Ang was increased. The mRNA and protein expressions of HIF-1α， VEGF， and TGF-β1 were increased to varying degrees （P<0.05）. Compared with the model group， the proliferation of connective tissue and inflammatory cell infiltration in the liver tissue of colchicine and Shugan Huazheng prescription groups were reduced. The content of HYP and Ang was decreased. The mRNA and protein expression levels of HIF-1α， VEGF， and TGF-β1 were decreased， and the colchicine group and high-dose group of Shugan Huazheng prescription were the most significant （P<0.05）. ConclusionShugan Huazheng prescription has an obvious therapeutic effect on CCl4-induced hepatic fibrosis model rats. Its therapeutic mechanism may be related to the regulation of the HIF-1α/VEGF/TGF-β1 signaling pathway and the improvement of hepatic hypoxia， vascular remodeling， and the syndrome of Qi deficiency and blood stasis in hepatic fibrosis.

Huanglian Jiedutang Regulates HIF-1α/VEGF Signaling Pathway to Improve Learning and Memory Abilities of APP/PS1 Transgenic Mice / 中国实验方剂学杂志

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg-1·d-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg-1·d-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.