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Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all Pï¼0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, Pï¼0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, Pï¼0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, Pï¼0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, Pï¼0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, Pï¼0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all Pï¼0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
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Carcinoma Pulmonar de Lewis , Dieta Baja en Carbohidratos , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Microambiente Tumoral , Animales , Carcinoma Pulmonar de Lewis/radioterapia , Carcinoma Pulmonar de Lewis/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Dieta Baja en Carbohidratos/métodos , Carga Tumoral , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologíaRESUMEN
The article "MicroRNA-199a regulates myocardial fibrosis in rats by targeting SFRP5", by M.-H. Chen, J.-C. Liu, Y. Liu, Y.-C. Hu, X.-F. Cai, D.-C. Yin, published in Eur Rev Med Pharmacol Sci 2019; 23 (9): 3976-3983-DOI: 10.26355/eurrev_201905_17827-PMID: 31115026 has been retracted by the authors. This paper has been questioned on PubPeer (https://pubpeer.com/publications/6417BECD38A43595A89D977A1CBDF8). In particular, concerns were raised about Figures 2C and 4C, potentially showing three panels with overlapping details of a single image. The corresponding author states they used the wrong figure during manuscript drafting, which led to picture reuse. For this reason, the authors decided to withdraw the manuscript. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17827.
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Pressure ulcers (PUs) are economically burdensome medical conditions. Early changes in pressure ulcers are associated with erythema. In this study, bioelectrical impedance was used to measure the differences between PUs and blanchable erythema. We divided 21 ICR mice into three groups: control, 1000 mmHg-1h, and 1000 mmHg-6h. Healthy skin, blanchable erythema, and PUs were induced on the dorsal skin. The results indicated an immediate increase in impedance, resistance, and reactance values in the pressure group after release, followed by a subsequent decrease until two days after release. Compared with the control group, impedance and reactance significantly increased by 30.9% (p < 0.05) and 30.1% (p < 0.01), respectively, in the 6 h-loading group immediately after release. One and two days after release, the 1 h-loading and 6 h-loading groups exhibited significantly different degrees of decline. One day after release, impedance and resistance decreased by 30.2% (p < 0.05) and 19.8% (p < 0.05), respectively, in the 1 h-loading group; while impedance, resistance, and reactance decreased by 39.2% (p < 0.01), 26.8% (p < 0.01), and 45.7% (p < 0.05), respectively, in the 6 h-loading group. Two days after release, in the 1 h-loading group, impedance and resistance decreased by 28.3% (p < 0.05) and 21.7% (p < 0.05), respectively; while in the 6 h-loading group, impedance, resistance, and reactance decreased by 49.8% (p < 0.001), 34.2% (p < 0.001), and 59.8% (p < 0.01), respectively. One and two days after release the pressure group reductions were significantly greater than those in the control group. Additionally, we monitored changes during wound healing. Distinguishing early PUs from blanchable erythema by noninvasive bioelectrical impedance technology may have applications value in early assessment of PUs.
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Modelos Animales de Enfermedad , Impedancia Eléctrica , Eritema , Ratones Endogámicos ICR , Úlcera por Presión , Cicatrización de Heridas , Animales , Úlcera por Presión/fisiopatología , Impedancia Eléctrica/uso terapéutico , Eritema/fisiopatología , Eritema/etiología , Ratones , Cicatrización de Heridas/fisiología , MasculinoRESUMEN
The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with GC across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Estudios de Seguimiento , Asia , Oncología Médica , Sociedades MédicasRESUMEN
Oxidative stress and inflammation have been implicated in hepatic fibrosis. Antioxidant and anti-inflammatory activities are among the pharmacological effects of hyperoside. This study aimed to evaluate the impact of hyperoside on hepatic fibrosis and elucidate the underlying processes that perpetuate this relationship. The findings indicated that hyperoside significantly protects mouse livers against damage, inflammation, and fibrosis. Specifically, attenuation of hepatic fibrosis is associated with lower expression of HMGB1 protein and reduced expression of Toll-like receptor 4, PARP-1, and nuclear factor-kB (NF-κB) p65 mRNA and protein. Furthermore, hyperoside inhibited the cytoplasmic translocation of HMGB1 and nuclear localization of NF-κB p65 in the hepatic tissues of mice. The results of this study indicate that hyperoside may impose a blocking or reversing effect on hepatic fibrosis; additionally, the corresponding hyperoside-dependent mechanism may be linked to PARP-1-HMGB1 pathway regulation.
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Proteína HMGB1 , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Tetracloruro de Carbono , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Inflamación , Adenosina Difosfato RibosaRESUMEN
Objective: To investigate anatomical morphology and classification of persistent descending mesocolon (PDM) in patients with left-sided colorectal cancer, as well as the safety of laparoscopic radical surgery for these patients. Methods: This is a descriptive study of case series. Relevant clinical data of 995 patients with left colon and rectal cancer who had undergone radical surgery in Fujian Medical University Union Hospital from July 2021 to September 2022 were extracted from the colorectal surgery database of our institution and retrospectively analyzed. Twenty-four (2.4%) were identified as PDM and their imaging data and intra-operative videos were reviewed. We determined the distribution and morphology of the descending colon and mesocolon, and evaluated the feasibility and complications of laparoscopic surgery. We classified PDM according to its anatomical characteristics as follows: Type 0: PDM combined with malrotation of the midgut or persistent ascending mesocolon; Type 1: unfixed mesocolon at the junction between transverse and descending colon; Type 2: PDM with descending colon shifted medially (Type 2A) or to the right side (Type 2B) of the abdominal aorta at the level of the origin of the inferior mesentery artery (IMA); and Type 3: the mesocolon of the descending-sigmoid junction unfixed and the descending colon shifted medially and caudally to the origin of IMA. Results: The diagnosis of PDM was determined based on preoperative imaging findings in 9 of the 24 patients (37.5%) with left-sided colorectal cancer, while the remaining diagnoses were made during intraoperative assessment. Among 24 patients, 22 were male and 2 were female. The mean age was (63±9) years. We classified PDM as follows: Type 0 accounted for 4.2% (1/24); Type 1 for 8.3% (2/24); Types 2A and 2B for 37.5% (9/24) and 25.0% (6/24), respectively; and Type 3 accounted for 25.0% (6/24). All patients with PDM had adhesions of the mesocolon that required adhesiolysis. Additionally, 20 (83.3%) of them had adhesions between the mesentery of the ileum and colon. Twelve patients (50.0%) required mobilization of the splenic flexure. The inferior mesenteric artery branches had a common trunk in 14 patients (58.3%). Twenty-four patients underwent D3 surgery without conversion to laparotomy; the origin of the IMA being preserved in 22 (91.7%) of them. Proximal colon ischemia occurred intraoperatively in two patients (8.3%) who had undergone high ligation at the origin of the IMA. One of these patients had a juxta-anal low rectal cancer and underwent intersphincteric abdominoperineal resection because of poor preoperative anal function. Laparoscopic subtotal colectomy was considered necessary for the other patient. The duration of surgery was (260±100) minutes and the median estimated blood loss was 50 (20-200) mL. The median number of No. 253 lymph nodes harvested was 3 (0-20), and one patient (4.2%) had No.253 nodal metastases. The median postoperative hospital stay was 8 (4-23) days, and the incidence of complications 16.7% (4/24). There were no instances of postoperative colon ischemia or necrosis observed. One patient (4.2%) with stage IIA rectal cancer developed Grade B (Clavien-Dindo III) anastomotic leak and underwent elective ileostomy. The other complications were Grade I-II. Conclusions: PDM is frequently associated with mesenteric adhesions. Our proposed classification can assist surgeons in identifying the descending colon and mesocolon during adhesion lysis in laparoscopic surgery. It is crucial to protect the colorectal blood supply at the resection margin to minimize the need for unplanned extended colectomy, the Hartmann procedure, or permanent stomas.
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Laparoscopía , Mesocolon , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Mesocolon/cirugía , Estudios Retrospectivos , Laparoscopía/métodos , Neoplasias del Recto/cirugía , Colectomía/métodos , IsquemiaRESUMEN
OBJECTIVE: Adult stem cell senescence and exhaustion are important drivers of organismal age. Restored stem cell self-renewal has revealed novel therapeutic targets for decreasing the incidence of age-associated diseases (AADs) and prolonging the human health span. Transient ectopic expression of the reprogramming factors Oct3/4, Sox2, Klf4 and c-Myc (collectively known as OSKM) in somatic cells can induce partial cellular reprogramming and effectively ameliorate their age-associated hallmarks. However, how this form of rejuvenation is applied to senescent stem cells remains unknown. MATERIALS AND METHODS: The Integrin-α6highCD71high epidermal stem cells (ESCs) with low self-renewal ability were sorted by flow cytometry and then treated by the interrupted reprogramming induced by transient expression of OSKM. The ability of secondary clones' generation and self-proliferation in vitro, as well as stem cell marker p63, were detected to determine their self-renewal ability. Besides, gene and protein of epidermal cell markers were detected to determine whether their cell identities were retained. Finally, DNA methylation age (eAge) and DNA dehydroxymethylase/methyltransferase were analyzed to explore the alternation of their global DNA methylation pattern during this rejuvenation. RESULTS: The partial reprogramming restored the youthful self-renewal and proliferation in senescent ESCs, including larger secondary clone generation, higher expression of stem cell marker p63 and proliferation marker Ki67, and faster proliferation speed, in each case without abolishing epithelial cellular identity. Moreover, the rejuvenation of adult stem cells could be maintained for 2 weeks after reprogramming factor withdrawal, which was more stable than that of differentiated somatic cells. Additionally, we found that partial reprogramming counteracted the acceleration of eAge in senescent epidermal stem cells and DNA methyltransferase 1 (DNMT1) may play a crucial role in this process. CONCLUSIONS: Partial reprogramming has high therapeutic potential for reversing adult stem cell age, providing an advanced way to treat AADs.
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Reprogramación Celular , Células Madre Pluripotentes Inducidas , Adulto , Humanos , Células Madre , Células Epidérmicas , Metiltransferasas/metabolismo , ADN/metabolismo , Células Madre Pluripotentes Inducidas/metabolismoRESUMEN
Objective: To investigate the clinical characteristics and the risk factors of severe human metapneumovirus (hMPV)-associated community acquired pneumonia (CAP) in children. Methods: A retrospective case summary was conducted. From December 2020 to March 2022, 721 children who were diagnosed with CAP and tested positive for hMPV nucleic acid by PCR-capillary electrophoresis fragment analysis of nasopharyngeal secretions at the Yuying Children's Hospital, the Second Affiliated Hospital of Wenzhou Medical University were selected as the research objects. The clinical characteristics, epidemiological characteristics and mixed pathogens of the two groups were analyzed. According to CAP diagnostic criteria, the children were divided into the severe group and the mild group. Chi-square test or Mann-Whitney rank and contrast analysis was used for comparison between groups, while multivariate Logistic regression was applied to analyze the risk factors of the severe hMPV-associated CAP. Results: A total of 721 children who were diagnosed with hMPV-associated CAP were included in this study, with 397 males and 324 females. There were 154 cases in the severe group. The age of onset was 1.0 (0.9, 3.0) years, <3 years old 104 cases (67.5%), and the length of hospital stay was 7 (6, 9) days. In the severe group, 67 children (43.5%) were complicated with underlying diseases. In the severe group, 154 cases (100.0%) had cough, 148 cases (96.1%) had shortness of breath and pulmonary moist rales, and 132 cases (85.7%) had fever, 23 cases (14.9%) were complicated with respiratory failure. C-reactive protein (CRP) was elevated in 86 children (55.8%), including CRP≥50 mg/L in 33 children (21.4%). Co-infection was detected in 77 cases (50.0%) and 102 strains of pathogen were detected, 25 strains of rhinovirus, 17 strains of Mycoplasma pneumoniae, 15 strains of Streptococcus pneumoniae, 12 strains of Haemophilus influenzae and 10 strains of respiratory syncytial virus were detected. Six cases (3.9%) received heated and humidified high flow nasal cannula oxygen therapy, 15 cases (9.7%) were admitted to intensive care unit, and 2 cases (1.3%) received mechanical ventilation. In the severe group, 108 children were cured, 42 children were improved, 4 chlidren were discharged automatically without recovery and no death occurred. There were 567 cases in the mild group. The age of onset was 2.7 (1.0, 4.0) years, and the length of hospital stay was 4 (4, 6) days.Compared with the mild group, the proportion of children who age of disease onset <6 months, CRP≥50 mg/L, the proportions of preterm birth, congenital heart disease, malnutrition, congenital airway malformation, neuromuscular disease, mixed respiratory syncytial viruses infection were higher (20 cases (13.0%) vs. 31 cases (5.5%), 32 cases (20.8%) vs. 64 cases (11.3%), 23 cases (14.9%) vs. 44 cases (7.8%), 11 cases (7.1%) vs. 18 cases (3.2%), 9 cases (5.8%) vs. 6 cases (1.1%), 11 cases (7.1%) vs. 12 cases (2.1%), 8 cases (5.2%) vs. 4 cases (0.7%), 10 cases (6.5%) vs. 13 cases (2.3%), χ2=0.42, 9.45, 7.40, 4.94, 11.40, 8.35, 3.52, 6.92, all P<0.05). Multivariate Logistic regression analysis showed that age<6 months (OR=2.51, 95%CI 1.29-4.89), CRP≥50 mg/L (OR=2.20, 95%CI 1.36-3.57), prematurity (OR=2.19, 95%CI 1.26-3.81), malnutrition (OR=6.05, 95%CI 1.89-19.39) were the independent risk factors for severe hMPV-associated CAP. Conclusions: Severe hMPV-associated CAP is most likely to occur in infants under 3 years old and has a higher proportion of underlying diseases and co-infection. The main clinical manifestations are cough, shortness of breath and pulmonary moist rales, fever. The overall prognosis is good. Age<6 months, CRP≥50 mg/L, preterm birth, malnutrition are the independent risk factors for severe hMPV-associated CAP.
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Coinfección , Infecciones Comunitarias Adquiridas , Desnutrición , Metapneumovirus , Neumonía Viral , Nacimiento Prematuro , Virus Sincitial Respiratorio Humano , Lactante , Masculino , Femenino , Humanos , Niño , Recién Nacido , Preescolar , Estudios Retrospectivos , Tos , Ruidos Respiratorios , Neumonía Viral/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología , Factores de Riesgo , DisneaRESUMEN
CRISPR/Cas(the clustered regularly interspaced short palindromic repeats-CRISPR associated)system exists in most bacteria and all archaea. It is an important strategy for bacteria and archaea to resist foreign nucleic acid invasion and use for self-defense. The CRISPR/Cas system is a simple, fast, and specific diagnostic tool, which is widely used in agriculture, industry, animal husbandry, and medicine. This article mainly introduces and discusses recently advantages and limitations of biosensors combining CRISPR/Cas system with fluorescence, visualization and surface enhanced raman related technologies, as well as future research directions.
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Bacterias , Sistemas CRISPR-Cas , Animales , Bacterias/genética , ArchaeaRESUMEN
BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Trastorno Bipolar , Trastorno Depresivo Mayor , Lupus Eritematoso Sistémico , Trastorno Obsesivo Compulsivo , Niño , Humanos , Masculino , Femenino , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/genética , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/genética , Trastorno Bipolar/epidemiología , Trastorno Bipolar/genética , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/genética , Trastorno Obsesivo Compulsivo/psicología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/psicología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/genéticaRESUMEN
Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.
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Lesiones Encefálicas , Paro Cardíaco , Daño por Reperfusión , Animales , Apoptosis , Estrés del Retículo Endoplásmico , Quinasas MAP Reguladas por Señal Extracelular , Paro Cardíaco/complicaciones , Masculino , ARN Mensajero , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismoAsunto(s)
COVID-19 , Leucopenia , Trombocitopenia , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2 , Trombocitopenia/inducido químicamenteAsunto(s)
COVID-19 , Embolia Pulmonar , Trombosis de la Vena , Vacunas contra la COVID-19 , Humanos , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/etiología , SARS-CoV-2 , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiologíaRESUMEN
This study aimed to detect the expression of Wnt-induced secreted protein-1 (WISP-1) in renal fibrosis (RF) and to clarify the underlying mechanism. An in vivo mousee model of unilateral ureteral obstruction (UUO) and in vitro model of fibrosis on renal tubular epithelial NRK52E cells after transforming growth factor-ß1 (TGF-ß1) stimulation were used. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and immunohistochemistry were used to detect WISP-1 and fibrosis markers, including the expression of fibronectin (FN), collagen I (Col I), collagen IV (Col IV), and α-smooth muscle actin (α-SMA). In vitro experiments showed that the expression of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in rat renal tubular epithelial cells were significantly higher than that in the control group after 48 h of TGF-ß1 stimulation. In vivo experiments showed that the expressions of WISP-1 and fibrosis markers FN, Col I, Col IV, and α-SMA in the obstructed kidney of UUO animal models were significantly increased in mRNA and protein levels compared to normal mice. This study showed that WISP-1 may be an essential cytokine that promotes renal fibrosis, being involved in the development of renal fibrosis.
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Enfermedades Renales , Animales , Biomarcadores , Fibrosis , Riñón/patología , Ratones , Ratas , Factor de Crecimiento Transformador beta1/genética , Obstrucción Ureteral , Proteínas Wnt , Proteína Wnt1RESUMEN
OBJECTIVE: The study developed mushroom stalk residues as feed additives in the broiler diet for improving the growth performance and immunity of broilers as well as to increase the value of mushroom stalk residues. METHODS: In total, 300 ROSS 308 broilers were randomly allocated into fifteen pens with five dietary treatments: i) control, basal diet; ii) CMWM, supplemented with 1% Cordyceps militaris waster medium (CM); iii) CMPE, supplemented with 0.5% CM+0.5% Pleurotus eryngii stalk residue (PE); iv) CMPS, supplemented with 0.5% CM+0.5% Pleurotus sajorcaju stalk residue (PS); v) CMFV, supplemented with 0.5% CM+0.5% Fammulina velutipes stalk residue (FV). RESULTS: The chemical analysis results showed that CM extracts, PE extracts, PS extracts, and FV extracts contain functional components such as polysaccharides and phenols and have both 2, 2-diphenyl-1-picryl-hydrazyl-hydrate scavenging and Ferrous scavenging capacities. The group CMWM saw increased body weight gain and feed conversion rate and the promotion of jejunum villus growth, but there is no significant difference in the intestinal bacteria phase. Antioxidant genes in the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)- antioxidant responsive element pathway among the groups are significantly higher than that of the control group, especially in group CMWM. CONCLUSION: The mushroom stalk residues have antioxidant functional components, can improve the intestinal health and body weight gain of chickens, and can activate the antioxidant pathway of Nrf2 to increase the heme oxygenase-1 expression. The treatment with 1% CM was the most promising as a feed additive.
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Rhopalosiphum padi is a worldwide agricultural pest. Chemosensory proteins (CSPs) are considered to be a type of transporters which can bind chemicals from external environments. Previous research showed that the expression of some insect CSPs were significantly increased after exposure to insecticides, and CSPs were involved in insecticide resistance or susceptibility. However, the role of CSPs in the susceptibility and response of R. padi to insecticides is still unknown. In this study, we identified eight CSP (RpCSP) from R. padi by genome-wide investigation. Seven RpCSP genes had two exons, while RpCSP7 had three exons. qPCR analyses showed that the mRNA levels of the eight RpCSP genes were significantly affected by imidacloprid and beta-cypermethrin in different post-treatment periods. Molecular docking predicted that there were hydrogen bonding sites which played key roles in binding of RpCSP4, RpCSP5, RpCSP6, RpCSP7 and RpCSP10 with imidacloprid and beta-cypermethrin. Knockdown of RpCSP4, RpCSP5, RpCSP6 and RpCSP10 by RNA interference significantly increased the aphid mortality under two sublethal concentrations of imidacloprid. Mortalities under two sublethal concentrations of beta-cypermethrin conditions were significantly higher after injection of R. padi with dsCSP4 and dsCSP6. The results indicate that some RpCSP genes are involved in the insecticide susceptibility of R. padi.
Asunto(s)
Áfidos/efectos de los fármacos , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Animales , Áfidos/química , Áfidos/genética , Proteínas de Insectos/genética , Insecticidas , Simulación del Acoplamiento Molecular , Neonicotinoides , Nitrocompuestos , Piretrinas , TriticumRESUMEN
AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.
Asunto(s)
Lipopolisacáridos , Periodontitis Periapical , Animales , Ácidos Grasos , Macrófagos , Ratones , Ratas , Proteína 1 de Unión a los Elementos Reguladores de EsterolesRESUMEN
Cognitive fatigue, or fatigue related to mental work, is a common experience. A growing body of work using functional neuroimaging has identified several regions that appear to be related to cognitive fatigue and that potentially comprise a "fatigue network". These include the striatum of the basal ganglia, the dorsolateral prefrontal cortex (DLPFC), the dorsal anterior cingulate cortex (dACC), the ventro-medial prefrontal cortex (vmPFC) and the anterior insula. However, no work has been conducted to assess whether the connectivity between these regions changes as a function of cognitive fatigue. We used a task-based functional neuroimaging paradigm to induce fatigue in 39 healthy individuals, regressed the signal associated with the task out of the data, and investigated how the functional connectivity between these regions changed as cognitive fatigue increased. We observed functional connectivity between these regions and other frontal regions largely decreased as cognitive fatigue increased while connectivity between these seeds and more posterior regions increased. Furthermore the striatum, the DLPFC, the insula and the vmPFC appeared to be central 'nodes' or hubs of the fatigue network. These findings represent the first demonstration that the functional connectivity between these areas changes as a function of cognitive fatigue.