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Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.
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ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 1.25-50 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.
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BACKGROUND: This study investigates the mediating effect of meaning in life between death anxiety and attitude toward palliative care among nursing students. METHODS: We enrolled 363 undergraduate nursing students using a convenience sampling method as the respondents and conducted a survey using general information about nursing students, the Chinese version of the FATCOD-B Scale, the Chinese version of the Death Anxiety Scale, and the Chinese version of the Meaning in Life Questionnaire. The SPSS25.0 statistical software was used to analyze the mediating effect. RESULTS: The mean total attitude score toward palliative care was (104.72 ± 10.62). Death anxiety had a significant negative predictive effect on the attitude toward palliative care (ß = -0.520, P < 0.01). When the mediating variable of the presence of meaning in life was included, the negative predictive effect of death anxiety on attitude toward palliative care remained significant (ß = -0.379, P = 0.036); the mediating effect (-0.141) accounted for 27.12% of the total impact (-0.520). CONCLUSIONS: The presence of meaning in life mediates the relationship between death anxiety and attitude toward palliative care. This implies that nursing educators, through their role in educating nursing students about the meaning of life, can significantly influence the development of a positive attitude toward palliative care.
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Ansiedad , Actitud Frente a la Muerte , Cuidados Paliativos , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Estudiantes de Enfermería/estadística & datos numéricos , Femenino , Masculino , Cuidados Paliativos/métodos , Cuidados Paliativos/psicología , Ansiedad/psicología , Encuestas y Cuestionarios , Adulto Joven , Adulto , Actitud del Personal de Salud , Bachillerato en Enfermería/métodos , Psicometría/instrumentación , Psicometría/métodosRESUMEN
OBJECTIVE: To investigate the diagnostic value of computed tomography (CT) and magnetic resonance imaging (MRI) in ovarian malignant mesothelioma (OMM). METHODS: The clinical and imaging data of 10 pathologically-confirmed OMM patients were analyzed retrospectively. RESULT: (1) The patients were 27 years to 70 years old, with an average age of 57.2 ± 15.4 years. Seven patients reported abdominal distension and pain, 1 reported lower abdominal discomfort and decreased appetite, and 2 patients had no symptoms. (2) Two cases of localized OMM with incomplete semi-annular "capsule" observed around the localized OMM tumors were reported while 8 cases had diffuse OMM in which the tumor parenchyma showed isointense or slightly hypointense on T1WI, inhomogeneous hyperintense on T2WI, and obviously hyperintense on DWI, with obvious inhomogeneous enhancement after enhancement. Diffuse OMM was not mainly composed of ovarian masses and was mainly characterized by mild ovarian enlargement, nodular and irregular thickening of the peritoneum, cloudy omentum, unclear fat gap, and reticular or irregular thickening, which can fuse into a "cake-shape". (3) All 10 patients underwent surgery, while 9 patients underwent systemic chemotherapy or immunotherapy after surgery. All patients with localized OMM survived. Out of the 8 diffuse-type patients, 5 died, 1 was lost to follow-up, and 2 survived. CONCLUSION: OMM has certain clinical and imaging characteristics. There is no liquefaction, calcification, or partition in the tumor. The ovarian enlargement in the diffuse lesion is not significant. The diffuse thickening of the peritoneum and omentum with early appearance of mural nodules and ascites in the upper abdomen, help the diagnosis of OMM.
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Mesotelioma Maligno , Neoplasias Ováricas , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Mesotelioma Maligno/diagnóstico por imagen , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/cirugía , Tomografía Computarizada por Rayos X/métodosRESUMEN
OBJECTIVE: We report a low-grade endometrial stromal sarcoma (ESS) with a novel CDKN1A-JAZF1 fusion gene arising from abdominal wall endometrioma. CASE REPORT: A 40-year-old woman presented with a 5.5-cm abdominal wall mass juxtaposed to the postoperative scar of two cesarean sections. Histologically, the tumor exhibited obvious tongue-like protrusions into the surrounding tissue, showed spindle cells with multinodular growth pattern that occasionally rotate around small arteries. Immunohistochemically, the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), negatively stained for smooth muscle actin (SMA), CD117, CyclinD1. In addition, a previously undescribed gene fusion between CDNK1A 5' end of exon 1(NM_000389.5) and JAZF1 3' end of exon 5 (NM_175,061,3) was reported in this case. CONCLUSION: This report of ESS suggesting that rapidly growing abdominal wall masses without menstruation-related should be promptly evaluated and treated aggressively. In addition, we have expanded the molecular landscape of low-grade ESS.
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Pared Abdominal , Neoplasias Endometriales , Tumores Estromáticos Endometriales , Endometriosis , Sarcoma Estromático Endometrial , Embarazo , Humanos , Femenino , Adulto , Sarcoma Estromático Endometrial/patología , Endometriosis/complicaciones , Endometriosis/genética , Endometriosis/patología , Cicatriz/complicaciones , Cicatriz/genética , Cicatriz/patología , Cesárea , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Proteínas de Neoplasias/genética , Tumores Estromáticos Endometriales/patología , Factores de Transcripción/genética , Fusión Génica , Proteínas de Unión al ADN/genética , Proteínas Co-Represoras/genética , Inhibidor p21 de las Quinasas Dependientes de la CiclinaRESUMEN
The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.
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Microbioma Gastrointestinal , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Disbiosis/terapia , Disbiosis/microbiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/metabolismoRESUMEN
BACKGROUND: Endometrial stromal tumours are uncommon tumours of the uterus. They mainly occur in perimenopausal women. Tumours with typical clinicopathological features do not usually pose diagnostic problems. However, rare clinicopathological features can occur, and clinicians without significant experience may have difficulty diagnosing these tumours and managing these patients. METHODS: Herein, we report a case of endometrial stromal sarcoma that occurred in a 25-year-old woman. The pathological features, immunophenotype, treatment and prognosis were discussed. RESULTS: The tumour revealed morphological heterogeneity, and there were similar proliferative-type endometrial stromal cells, an extensive amount of mature adipose tissue, and prominent rhabdomyoblastic and smooth muscle cells. Histopathological and immunohistochemical studies confirmed low-grade endometrial stromal sarcoma with smooth muscle, adipocytic and rhabdomyoblastic differentiation (approximately 60% were differentiated tissues). The final treatment of the tumour was total abdominal hysterectomy with bilateral salpingo-oophorectomy. There was no evidence of recurrence for 109 months postoperatively. CONCLUSIONS: We found that low-grade endometrial stromal tumours with extensive adipocytic and prominent rhabdomyoblastic differentiation are misdiagnosed because they are infrequent. They must be differentiated from rhabdomyosarcoma with accurate identification of adipocytes, and long-term follow-up is needed.
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Neoplasias Endometriales , Tumores Estromáticos Endometriales , Sarcoma Estromático Endometrial , Adulto , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/cirugía , Tumores Estromáticos Endometriales/diagnóstico , Tumores Estromáticos Endometriales/patología , Tumores Estromáticos Endometriales/cirugía , Femenino , Humanos , Pronóstico , Sarcoma Estromático Endometrial/diagnóstico , Sarcoma Estromático Endometrial/patología , Sarcoma Estromático Endometrial/cirugíaRESUMEN
Naringin is one of the natural flavonoids extracted from many Chinese medicines. It ameliorates endothelial dysfunctions in atherosclerosis, diabetes, and cardiovascular diseases through free radical scavenging and antioxidant activities. The aim of the present study was to investigate the protective effects of naringin against pulmonary endothelial permeability in addition to airway inflammation in lipopolysaccharide/cigarette smoke (LPS/CS)-induced chronic obstructive pulmonary disease (COPD) mice.The COPD mice were exposed to LPS twice through intranasal inhalation and then to cigarette smoke daily for 6 weeks. The mice were orally administrated with naringin at doses of 40 or 80 mg/kg one hour before cigarette smoke exposure since the first day of the experiment. Naringin significantly alleviated pulmonary histopathological injury, and suppressed inflammatory cell infiltration and cytokine release in bronchoalveolar lavage fluid. Naringin decreased fluorescence intensity of Evans Blue in the lung tissues, and elevated the expression levels of tight junctional proteins. Meanwhile, naringin decreased neutrophil/lymphocyte/platelet counts and MDA content in blood, and upregulated Aquaporin1 (AQP1) in the lung tissues. However, the effect of naringin on airway inflammation and pulmonary endothelial permeability was inhibited in LPS/CS-treatment AQP1 deficiency mice. These results indicated that naringin attenuated LPS/CS-induced airway inflammatory and pulmonary hyperpermeability via upregulating AQP1 expression.
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Fumar Cigarrillos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Líquido del Lavado Bronquioalveolar , Modelos Animales de Enfermedad , Flavanonas , Inflamación/tratamiento farmacológico , Lipopolisacáridos/farmacología , Pulmón , Ratones , Ratones Endogámicos C57BL , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , NicotianaRESUMEN
Codonopsis lanceolata is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in C. lanceolata and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of C. lanceolata polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3ß, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in C. lanceolata. CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Codonopsis , Medicamentos Herbarios Chinos/farmacología , Disbiosis/tratamiento farmacológico , Fitoterapia/métodos , Polímero Poliacetilénico/farmacología , Animales , Apoptosis/efectos de los fármacos , Humanos , Masculino , Ratones Desnudos , Raíces de Plantas/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.
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Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-ß1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1ß-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentration-dependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-ß1, Smad3, Col I, α-SMA and TNF-α, and downregulated protein expressions of α-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-α and IL-6 in BALF, and TGF-ß1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, α-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-ß1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/NF-κB pathway.
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Antifibróticos/uso terapéutico , Proteína Forkhead Box O1/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Sesquiterpenos/uso terapéutico , Animales , Antifibróticos/aislamiento & purificación , Fibroblastos/efectos de los fármacos , Técnica del Anticuerpo Fluorescente , Proteína Forkhead Box O1/antagonistas & inhibidores , Humanos , Inula/química , Masculino , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Fibrosis Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Sesquiterpenos/aislamiento & purificación , Transducción de Señal/efectos de los fármacosRESUMEN
Long noncoding RNAs (lncRNAs) have been reported to participate in regulating many biological processes, including immune response to influenza A virus (IAV). However, the association between lncRNA expression profiles and influenza infection susceptibility has not been well elucidated. Here, we analyzed the expression profiles of lncRNAs, miRNAs, and mRNAs among IAV-infected adult rat (IAR), normal adult rat (AR), IAV-infected junior rat (IJR), and normal junior rat (JR) by RNA sequencing. Compared with differently expressed lncRNAs (DElncRNAs) between AR and IAR, 24 specific DElncRNAs were found between IJR and JR. Then, based on the fold changes and P value, the top 5 DElncRNAs, including 3 upregulated and 2 downregulated lncRNAs, were chosen to establish a ceRNA network for further disclosing their regulatory mechanisms. To visualize the differentially expressed genes in the ceRNA network, GO and KEGG pathway analysis was performed to further explore their roles in influenza infection of junior rats. The results showed that the downregulated DElncRNA-target genes were mostly enriched in the IL-17 signaling pathway. It indicated that the downregulated lncRNAs conferred the susceptibility of junior rats to IAV via mediating the IL-17 signaling pathway.
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Virus de la Influenza A/patogenicidad , MicroARNs/genética , Infecciones por Orthomyxoviridae/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Perfilación de la Expresión Génica , Virus de la Influenza A/aislamiento & purificación , Interleucina-17/genética , Interleucina-17/inmunología , MicroARNs/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/patología , Infecciones por Orthomyxoviridae/virología , ARN Largo no Codificante/inmunología , ARN Mensajero/inmunología , Ratas , Ratas Sprague-DawleyRESUMEN
Acute lung injury (ALI) is a life-threatening clinical syndrome with high morbidity and mortality. The main pathological features of ALI are increased alveolar-capillary membrane permeability, edema, uncontrolled migration of neutrophils to the lungs, and diffuse alveolar damage, resulting in acute hypoxemic respiratory failure. Glucocorticoids, aspirin, and other anti-inflammatory drugs are commonly used to treat ALI. Respiratory supports, such as a ventilator, are used to alleviate hypoxemia. Many treatment methods are available, but they cannot significantly ameliorate the quality of life of patients with ALI and reduce mortality rates. Herbal active ingredients, such as flavonoids, terpenoids, saponins, alkaloids, and quinonoids, exhibit advantages for ALI prevention and treatment, but the underlying mechanism needs further study. This paper summarizes the role of herbal active ingredients in anti-ALI therapy and progresses in the understanding of their mechanisms. The work also provides some references and insights for the discovery and development of novel drugs for ALI prevention and treatment.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/prevención & control , Fitoquímicos/uso terapéutico , Humanos , Fitoquímicos/química , Fitoquímicos/farmacologíaRESUMEN
PURPOSE: Plant-derived exogenous microRNAs (miRNAs) regulate human physiological functions by blocking the translation of target mRNAs. Although several computational approaches have been developed to elucidate the interactions of cross-species miRNAs and their targets in mammals, the number of verified plant miRNAs is still limited, and the biological roles of most exogenous plant miRNAs remain unknown. METHODS: A miRNA mimic library-based phenotypic screening, which contained 8394 plant mature miRNAs published in the official database miRbase, was performed to identify more novel bioactive plant miRNAs for the prevention of hepatic fibrosis. Inhibition of candidates for the activation of hepatic stellate cells (HSCs) and the underlying mechanisms were evaluated in TGF-ß1- and PDGF-exposed HSC models. The protective effects of the candidates against CCl4-induced liver fibrosis were evaluated in a mouse model. RESULTS: Among the 8394 plant mature miRNAs reported in the official database miRBase, five candidates were found to effectively inhibit the differentiation of HSCs. gma-miR-159a (miR159a) exerted the strongest inhibitory activities on both TGF-ß1- and PDGF-induced HSC activation and proliferation by inhibiting the GSK-3ß-mediated NF-κB and TGF-ß1 pathways. Moreover, miR159a was mainly accumulated in the liver after intravenous injection, and it reduced CCl4-induced hepatic fibrosis and inflammation in mice. CONCLUSION: Results indicated that miR159a has the therapeutic potential for preventing hepatic fibrosis. This study provides a novel strategy for achieving natural nucleic acid drugs.
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The increased resistance and toxicity have become the main causes of chemotherapy failure for treating lung cancer. The combination of chemotherapeutic drugs with other agents has been recognized as a promising strategy to overcome these difficulties. Isovitexin (IVT) is a well-known flavone C-glycoside found in many plants and has attracted wide attention due to its obvious antitumor and antioxidant effects. In this study, we investigated the synergistic effects of IVX and cisplatin (DDP) in non-small cell lung cancer (NSCLC) A549 and H1975 cells. The results showed that the combined treatment with IVT and DDP markedly inhibited proliferation and induced apoptosis of the two NSCLC cells. Using a mouse model of A549 xenograft, IVT potentiated the inhibition of DDP on tumor growth, but reduced DDP-induced hepatotoxicity and nephrotoxicity in mice. Remarkedly, IVT promoted lipopolysaccharide (LPS)- and lectin- stimulated splenocyte proliferation, and enhance cytotoxic T lymphocyte (CTL) and natural killer (NK) cell activities as well as the production of IL-2 and TNF-α. Furthermore, IVT significantly reduced glucose uptake, lactate production, and ATP production, and downregulated the protein expressions of pyruvate kinase M2 (PKM2)-mediated pathway in both A549 and H1975 cells. After the over-expression of PKM2 in the NSCLC cells, the synergistic antitumor effect of IVT and DDP was markedly weakened. Therefore, IVT not only inhibited cell proliferation and glucose metabolism via downregulating the expression of PKM2 to enhance the antitumor activity of DDP against lung cancer cells, and improved DDP-induced immunotoxicity in mice. It also presented a novel strategy to enhance the anti-tumor effect of platinum-based chemotherapy against NSCLC.
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Antineoplásicos/uso terapéutico , Apigenina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Glucosa/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Animales , Antineoplásicos/farmacología , Apigenina/farmacología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proteínas Portadoras/inmunología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Citocinas/inmunología , Regulación hacia Abajo/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Ácido Láctico/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Proteínas de la Membrana/inmunología , Ratones Desnudos , Linfocitos T Citotóxicos/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Hormonas Tiroideas/inmunología , Proteínas de Unión a Hormona TiroideRESUMEN
Russula griseocarnosa is one of the uncultivable important mycorrhizal edible fungi. Currently, there is a limited insight into the dynamic composition of the microbial communities associated with Russula. Here, the microbiota in the root and mycorrhizosphere from Russula-Fagaceae nature areas of Fujian province were identified by Illumina MiSeq high-throughput sequencing. First, we compared three types of fungal communities associated with Russula-Fagaceae root mycelia-running stage (stage-1), Russula sporocarping stage-2 (stage-2) and Russula-free Fagaceae root (stage-3). Fungal diversity negatively correlated with Russula. Russula, Tomentella and Lactarius were core EcM in Fagaceae roots. A total of eight genera, including Boletus, are likely a positive indicator of Russula sporocarp production in Russula-Fagaceae roots, while Tomentella and Elaphomyces for Russula symbiosis. Secondly, analysis of fungal and bacterial communities within rhizosphere soils from the three stages revealed six genera, including Dacryobolus and Acidocella, as possible indicator species associated with sporocarping in Russula. Elaphomyces, Tomentella, Sorangium, Acidicaldus, Acidobacterium and Haliangium occurred more frequently in the Russula rhizosphere. Furthermore, operational taxonomic unit (OTU) network analysis showed a positive correlation between Russula,Tomentella, Elaphomyces and Sorangium. Overall, our results revealed a relationship between micro-community and Russula, which may provide a new strategy for improving Russula symbiosis and sporocarp production.
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Basidiomycota , Biodiversidad , Microbiota , Micorrizas , Simbiosis , Bacterias/clasificación , Bacterias/genética , China , Hongos/clasificación , Hongos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota/fisiología , Micorrizas/clasificación , Micorrizas/genética , Raíces de Plantas/microbiología , Microbiología del SueloRESUMEN
PURPOSE: Abnormal glycolysis of immune cells contributed to the development of inflammatory response. Inhibition of this Warburg phenotype could be a promising strategy for preventing various inflammatory diseases. Iridin (IRD) is a natural isoflavone, and exerts anticancer, antioxidant, and anti-inflammatory effects. However, the underlying mechanism of IRD on acute inflammation remains unknown. In this study, the protective effects of IRD against lipopolysaccharide (LPS)-induced inflammation were investigated in murine macrophage RAW264.7 cells and in mice. METHODS: The inhibition of IRD on NO production in culture medium was detected by Griess assay while the levels of TNF-α, IL-1ß, and MCP-1 were detected by ELISA assay. The effects of IRD on OCR and ECAR levels in LPS-treated macrophages were monitored by using Seahorse Analyzer. The apoptosis rate as well as the release of ROS and NO of RAW264.7 cells were analyzed by flow cytometric assay. The protective effects of IRD were investigated on LPS-induced inflammation in mice. The expressions of PKM2 and its downstream (p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2) in cells and in lung tissues were detected by Western blotting analysis. RESULTS: IRD treatment at the concentrations of 12.5-50 µM significantly inhibited the productions of TNF-α, IL-1ß, MCP-1, and ROS, and suppressed the levels of glucose uptake and lactic acid in LPS-treated RAW264.7 cells. Oral administration with IRD (20-80 mg/kg) inhibited LPS-induced acute lung injury as well as inflammatory cytokine production in mice. Moreover, IRD targeted pyruvate kinase isozyme type M2 (PKM2) and suppressed its downstream p-JAK1, p-STAT1, p-STAT3, p-p65, iNOS, and COX2, which could be abolished by PKM2 agonist DASA-58 and antioxidant N-acetyl-L-cysteine, but partly be reversed by NF-κB activator CUT129 and JAK1 activator RO8191. CONCLUSION: IRD alleviated LPS-induced inflammation through suppressing PKM2-mediated pathways, and could be a potential candidate for the prevention of inflammatory diseases.
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Multiple agrometeorological disaster (MAD) occurs simultaneously in maize production. In order to ascertain the occurrence regularity and characteristics of MAD of maize in Liaoning Pro-vince, we defined and classified MAD, identified MAD of 50 meteorological stations in the maize growing season of Liaoning Province from 1961 to 2017, and examined the effects of MAD on maize yield in typical years. The results showed that the occurrence range of MAD was higher in most years from 1961 to 2017 than that of single agrometeorological disaster (SAD), and that the occurrence frequency of MAD was higher in most areas than that of SAD. The major MAD in Liaoning Province was drought in multiple periods (M1-D), followed by the combination of drought and delayed cold damage (M2-DC). The occurrence range of M1-D showed an upward trend from 1961 to 2017, whereas other MAD types showed a downward trend. After analyzing the occurrence of MAD in the typical years of maize yield reduction, we found that the occurrence frequency of M1-D and M2-DC was higher.
Asunto(s)
Desastres , Zea mays , China , Cambio Climático , SequíasRESUMEN
Platelets have been proved to exacerbate influenza infection and its complications. Inhibition of platelet activation may be a feasible method for preventing severe infection and secondary acute lung injury (ALI). Isofraxidin (IFD) is a natural coumarin isolated from the plants Sarcandra glabra and Siberian ginseng, and exerts anticancer, antioxidant and antiinflammatory effects. In the present study, we examined the therapeutic effects of IFD in ADP- or arachidonic acid (AA)-induced platelet aggregation model and in influenza A virus (IAV)-induced ALI mouse model. The results showed that IFD significantly inhibited platelet aggregation induced by ADP and AA in vitro in a concentration-dependent manner as well as the release of soluble P-selectin and platelet factor 4. Moreover, IFD significantly relieved IAV-induced lung inflammation, reduced the expressions of platelet activation biomarkers (P-selectin and CD61), decreased the serum levels of TNF-α, IL-1ß, IL-6 and MIP-2, suppressed peripheral platelet aggregation and prolonged the survival time of infected mice. The western blotting results also demonstrated that IFD reduced the phosphorylation levels of PI3K, AKT and p38 in the activated platelets stimulated by ADP and IAV infection. But IFD did not have any effects on IAV replication. It indicated that IFD ameliorated IAV-induced severe lung damage and lethal infection by suppressing platelet aggregation via regulating PI3K/AKT and MAPK pathways.