Meta-analysis of the adoption of omalizumab in the treatment of pediatric allergic diseases.

Introduction: Allergic diseases are common chronic conditions in children, omalizumab has a wide range of adoptions in various diseases. A meta-analysis was implemented to demonstrate the efficacy of omalizumab in the therapy of pediatric allergic diseases. Materials and methods: English databases were searched. The search terms included "Omalizumab", "Children", "Allergic asthma", and "Atopic dermatitis". The literature was screened regarding inclusion and exclusion criteria, and data were extracted and analyzed using RevMan5.3. Results: a total of six suitable studies, comprising 2761 patients, were selected for inclusion. The meta-analysis results implied that at 24 weeks, OR for worsening of symptoms in children was 0.10 (95 % confidence interval [CI] 0.03-0.41), Z = 3.24, P = 0.001 (P < 0.05); at 52 weeks, OR was 0.27 (95 % CI 0.09-0.83), Z = 2.28, P = 0.02 (P < 0.05); and during treatment, OR for adverse events in children was 0.87 (95 % CI 0.60-1.29), Z = 0.68, P = 0.49 (P > 0.05). Conclusion: the study comprised six investigations that examined the effectiveness of omalizumab in treating pediatric allergic diseases. The findings demonstrated that, in comparison to standard treatment, omalizumab can greatly alleviate allergy-related clinical symptoms in children, slow down disease progression, and has a higher safety profile with fewer adverse reactions. These results have practical implications and highlight the potential value of omalizumab in pediatric allergy treatment.

Development and validation of nomogram for predicting the cancer-specific survival among patients aged 80 and above with early-stage non-small cell lung cancer.

BACKGROUND: The use of nomograms in predicting the prognosis of early-stage non-small cell lung cancer (NSCLC), particularly in elderly patients, is not widespread. A validated prognostic model specifically for NSCLC patients over 80 years old holds promising potential for clinical application in forecasting patient outcomes. METHODS: The prognostic value of various factors for NSCLC patients aged 80 and above was evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2017). Kaplan-Meier (KM) curves, Cox proportional hazards regression models, and nomogram were utilized to evaluate the impact of each factor on cancer-specific survival (CSS). RESULTS: A cohort comprising 7045 individuals was selected for inclusion in the analysis. Through rigorous statistical analysis, 10 independent prognostic factors were identified and incorporated into the nomogram. The nomogram's receiver operating characteristic (ROC) curve area under the curve (AUC) was higher than that of the AJCC 7th edition TNM staging system's predicted CSS (0.744 versus 0.602), establishing the superior prognostic value of the nomogram. CONCLUSIONS: We have successfully created a highly accurate and discriminative nomogram that enables oncologists to predict the survival outcome of each individual patient with I/II NSCLC who is 80 years or older.

von Willebrand factor: more than a regulator of hemostasis and thrombosis.

von Willebrand factor (vWF) was first identified as an adhesive glycoprotein involved in hemostasis by Zimmermann in 1971. Since then, vWF has been shown to play a vital role in platelet adhesion, platelet binding to collagen and factor VIII protection. Recent studies have implicated vWF as a regulator of angiogenesis, smooth muscle cell proliferation, tumor cell metastasis and crosstalk in the immune system. In this review, we will discuss the aspects of vWF structure that facilitate its biological effects and speculate on its newly discovered and hypothesized roles in the pathogenesis of several diseases.

c-Jun promotes the survival of H9c2 cells under hypoxia via PTEN/Akt signaling pathway.

Ischemia and hypoxia are common pathophysiological characteristics in cardiovascular diseases. c-Jun expression could be induced by extra- or intracellular stimuli and plays a pivotal role in regulating cell survival in response to the stress. However, previous studies of c-Jun in cell proliferation and apoptosis showed conflicting results. In the present study, we demonstrated that the expression of c-Jun was induced by hypoxia in H9c2 cells. Loss of function of c-Jun was investigated by CCK-8, LDH, and TUNEL assays in low oxygen (1% O2) conditions. We revealed that c-Jun could promote cell survival and inhibit cell apoptosis under hypoxia. Knockdown of c-Jun also promoted the expression of apoptosis-related proteins under hypoxia, such as cleaved caspase-3, cleaved caspase-9, Bax, and Bim. Furthermore, we demonstrated that the knockdown of c-Jun inhibited the PTEN/Akt signaling pathway under hypoxia. Our findings suggested that c-Jun protected H9c2 cells from apoptosis and promoted the survival of H9c2 cells under hypoxia via PTEN/Akt signaling pathway.

Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress.

Sirtuin 1 (Sirt1) exerts its cardioprotective effects in various cardiovascular diseases via multiple cellular activities. However, the therapeutic implications of Sirt1 in hypoxic cardiomyocytes and the underlying mechanisms remain elusive. The present study investigated whether Sirt1 regulates autophagy and apoptosis in hypoxic H9C2 cardiomyocytes and in an experimental hypoxic mouse model. Right ventricular outflow tract biopsies were obtained from patients with cyanotic or acyanotic congenital heart diseases. Adenovirus Ad­Sirt1 was used to activate Sirt1 and Ad­Sh­Sirt1 was used to inhibit Sirt1 expression in H9C2 cells, in order to investigate the effect of Sirt1 on cellular autophagy and apoptosis. SRT1720, a pharmacological activator of Sirt1 and EX­527, a Sirt1 antagonist, were administered to mice to explore the role of Sirt1 in hypoxic cardiomyocytes in vivo. The levels of autophagy and apoptosis­related proteins were evaluated using western blotting. Apoptosis was investigated by TUNEL staining and Annexin V/7­aminoactinomycin D flow cytometry analysis. Heart tissue samples from cyanotic patients exhibited increased autophagy and apoptosis, as well as elevated Sirt1 levels, compared with the noncyanotic control samples. The data from the western blot analysis revealed that Sirt1 promoted autophagic flux and reduced apoptosis in hypoxic H9C2 cells. In addition, Sirt1 activated AMP­activated protein kinase (AMPK), and the AMPK inhibitor Compound C abolished the effect of Sirt1 on autophagy activation. Further exploration of the mechanism revealed that Sirt1 protects hypoxic cardiomyocytes from apoptosis, at least in part, through inositol requiring kinase enzyme 1α (IRE1α). Consistent with the in vitro results, treatment with the Sirt1 activator SRT1720 activated AMPK, inhibited IRE1α, enhanced autophagy, and decreased apoptosis in the heart tissues of normoxic mice compared with the hypoxia control group. Opposite changes were observed in hypoxic mice treated with the Sirt1 inhibitor EX­527. These results suggested that Sirt1 promoted autophagy via AMPK activation and reduced hypoxia­induced apoptosis via the IRE1α pathway, to protect cardiomyocytes from hypoxic stress.

AMPK activation serves a critical role in mitochondria quality control via modulating mitophagy in the heart under chronic hypoxia.

Mitochondrial biogenesis is one of the generally accepted regulatory mechanisms in the heart under chronic hypoxia. The precise quantity and quality control of mitochondria is critical for the survival and function of cardiomyocytes. Mitochondrial autophagy, also known as mitophagy, which selectively eliminates dysfunctional and unwanted mitochondria, is the most important type of mitochondrial quality control. However, the detailed molecular mechanisms of mitophagy in cardiomyocytes have been largely undefined. The present study investigated the role of adenosine 5'­monophosphate­activated protein kinase (AMPK) in mitophagy regulation in cardiomyocytes under chronic hypoxia. H9c2 cells were cultured under hypoxic conditions (1% O2) for different time periods. Mitochondrial biogenesis was confirmed and hypoxia was found to induce the collapse of mitochondrial membrane potential (ΛΨm) and increase the number of dysfunctional mitochondria. As expected, mitochondrial autophagy was increased significantly in cardiomyocytes exposed to hypoxic conditions for 48 h. AMPK was activated under hypoxia. Notably, when the activation of AMPK was enhanced by the AMPK agonist AICAR, mitochondrial autophagy was increased accordingly. By contrast, when AMPK activation was blocked, mitochondrial autophagy was decreased and cardiomyocyte apoptosis was increased. In conclusion, in the present study, mitophagy was activated and played a crucial role in cardioprotection under chronic hypoxia. AMPK was involved in mitophagy regulation, thereby providing a potential therapeutic target for heart diseases associated with chronic hypoxia.

Melatonin alleviates hypoxia-induced cardiac apoptosis through PI3K/Akt pathway.

Hypoxia-induced apoptosis is an inevitable problem in cyanotic congenital heart disease. In the present study, we investigated effects of melatonin on hypoxic cardiomyocytes in vitro and in vivo, and explored its underlying mechanism. H9C2 cells were subjected to hypoxia for 48 hours. Mice were subjected to hypoxia treatment (10% O2) for 4 weeks. Cell viability was detected by the cell counting kit-8 assay. Cellular apoptosis was assessed by Annexin V/7 AAD assay. Western blotting was employed to determine the expression of Bcl-2, Bax, cleaved caspase 3, phosphorylation of PI3K, and AKT. Melatonin increased cell viability and alleviated apoptosis in hypoxic H9C2 cells and cardiomyocytes of hypoxia-treated mice. Melatonin pretreatment increased Bcl-2 and decreased cleaved caspase 3 and Bax levels. Moreover, melatonin activated the PI3K/Akt pathway. The protective effects of melatonin were abolished by a PI3K/Akt-inhibitor, LY294002. Our results demonstrated that melatonin confers cardioprotection by inhibiting apoptosis through the activation of PI3K/Akt signaling pathway in hypoxic cardiomyocytes.

Cardiac resident macrophages are involved in hypoxia­induced postnatal cardiomyocyte proliferation.

Induction of cardiomyocyte proliferation, the most promising approach to reverse myocardial attrition, has been gaining importance as a therapy for cardiovascular disease. Hypoxia and macrophages were previously independently reported to promote cardiomyocyte proliferation in mice. However, whether hypoxia promotes cardiomyocyte proliferation in humans, and the association between hypoxia and macrophages in cardiomyocyte proliferation, have not to the best of our knowledge been previously investigated. The present study investigated the cardiomyocyte proliferation in 22 acyanotic and 29 cyanotic patients. Cardiomyocyte proliferation in a hypoxic mouse model (15% O2) was subsequently performed and the macrophage subsets were analyzed. A C­C chemokine receptor type 2 (CCR2) inhibitor was used to increase the number of resident macrophages in order to investigate the effect of macrophages on cardiomyocyte proliferation. The results demonstrated that cardiomyocyte proliferation in the cyanotic infant group was significantly increased compared with the acyanotic infant group and the hypoxia­treated C57BL/6J neonates confirmed the hypoxia­induced cardiomyocyte proliferation. However, hypoxia did not induce the proliferation of isolated cardiomyocytes. Notably, hypoxia treatment increased the number of cardiac resident macrophages in neonate hearts. Furthermore, increasing the number of resident macrophages significantly enhanced cardiomyocyte proliferation. In conclusion, postnatal hypoxia promoted cardiomyocyte proliferation in humans and animals, and cardiac resident macrophages may be involved in this process. Therefore, this novel mechanism may provide a promising strategy for cardiovascular disease treatment.