•The expression of ICAM-1 in Human Umbilical Vein Endothelial Cells (HUVECs) was enhanced by HA of H1N1 alone instead of whole H1N1 virus.•The expression of IL-6 in Human Umbilical Vein Endothelial ...Cells (HUVECs) was also enhanced by.•HA of H1N1 alone instead of whole H1N1 virus induced pathological injury in lung tissues of the mice.•HA-targeted agents may be potential anti-influenza drugs.
Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated.
RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively.
After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 μg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 μl of HA (50 μg/ml and 100 μg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion.
HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.
To investigate the incidence of complications and types of chemoradiotherepy induces symptom clusters in patients with nasopharyngeal carcinoma (NPC) who were first diagnosed after treatment and ...discharged from hospital.
After their discharge home, 130 NPC patients who had been treated with chemoradiotherapy were asked to complete a modified Chinese version of the
developed by the European Organization for the Research and Treatment of Cancer in the Head and Neck. Symptom clusters in patients were identified through exploratory factor analysis.
The most serious symptoms for discharged NPC patients who had received chemoradiotherapy were dental problems, a sense of obstruction while swallowing, embarrassment in physical contact with family members and friends, difficulty in speaking with others, and embarrassment in public. The six symptom clusters identified through exploratory factor analysis were (1) painful eating, (2) social difficulties, (3) psychological disorders, (4) symptomatic shame, (5) teeth/throat injuries, and (6) sensory abnormalities. The total contribution rate of variance was 65.73%.
NPC patients who are treated with chemoradiotherapy can experience adverse symptom clusters that continue after discharge. Nurses should evaluate the patients' symptoms before discharge and provide targeted health education services which would reduce the patients' complications and improve the quality of life at home. Besides, medical staff should evaluate the complications in a timely and comprehensive manner and provide individualized health education for the affected patients to help them manage chemoradiotherapy side effects.
Transforming growth factor-β1 (TGF-β1) and -β2 are correlated with poorer prognosis in gastric cancer (GC), which act in both tumor and immune cells. However, their expressions in precancer and ...tumor-cell interactions with peripheral blood mononuclear cells (PBMCs) remain unclear. Protein levels of TGF-β1 and -β2 were analyzed by immunohistochemistry and corresponding mRNA levels were determined by quantitative real-time polymerase chain reaction in 93 surgical and biopsy specimens. Serum TGF-β concentration was detected by enzyme-linked immunosorbent assays. AGS and MKN45 cell lines were directly or indirectly cocultured with PBMCs in vitro. TGF-β and Smad molecules were detected after cocultures and the growths of GC cells and PBMCs were assessed by cell proliferation assay. The results showed positive staining for TGF-β1 was detected in 20% of control samples, 52.3% of precancer, 59.1% of early GC and 66.7% of advanced GC samples, correlated with lesion progression (χ² = 9.487, P = 0.002). All tissues were positive for TGF-β2. TGF-β1 mRNA levels were increased in advanced cancers, while TGF-β2 increased earlier. TGF-β1 mRNA levels were higher in tumor than in peritumor, which positively correlated with Smad2 and Smad7. Serum TGF-β levels were significantly higher in patients with early and advanced cancers compared to controls (TGF-β1∶50.08±4.38 and 45.76±5.00 vs. 27.78±6.11 ng/mL; TGF-β2∶133.61±21.90 and 111.34±15.76 vs. 59.41±15.42 ng/mL, both P<0.05). The levels of TGF-β1 mRNA and cytokine secretion were higher in GC cells after direct coculture compared to indirect culture. TGF-β1 was decreased and TGF-β2 was increased in PBMCs after cocultures. Moreover, TGF-β1 inhibited the viability of PBMCs but not cancer cells. Collectively, neoplastic transformation may be an early event involving the increase of TGF-β1 in the general and local environment. TGF-β1 production is promoted by the direct interaction between GC cells and PBMCs, which might facilitate cancer development.
The burden of cancer-related mortality of common malignancies has been reported worldwide. However, whether bone cancer (BC), as a highly aggressive and heterogeneous group of rare cancers, followed ...a similar or distinct epidemiological pattern during such process remains largely unknown. We aimed to analyze the mortality and the temporal trends of BC in relation to gender, age, and premature death in Shanghai, China.
We conducted a population-based analysis of the mortality data of BC in Shanghai Pudong New Area (PNA) from 2005 to 2020. The epidemiological characteristics and long-term trends in crude mortality rates (CMRs), age-standardized mortality rates worldwide (ASMRWs), and rate of years of life lost (YLL) was analyzed using the Joinpoint regression program. The demographic and non-demographic factors affecting the mortality rate were evaluated by the decomposition method.
There are 519 BC-specific deaths accounting for 0.15% of all 336,823 deaths and 0.49% of cancer-specific death in PNA. The CMR and ASMRW of BC were 1.15/10
person-year and 0.61/10
person-year, respectively. The YLL due to premature death from BC was 6,539.39 years, with the age group of 60-69 years having the highest YLL of 1,440.79 years. The long-term trend of CMR, ASMRW, and YLL rate significantly decreased by -5.14%, -7.64%, and -7.27%, respectively, per year (all
< 0.05) in the past 16 years. However, the proportion of BC-specific death within the total cancer-specific death dropped to a plateau without further improvement since 2016, and a remarkable gender and age disparity was noticed in the observed reduction in mortality. Specifically, the elderly benefited less but accounted for a larger percentage of BC population in the last decades. Although the overall mortality of BC decreased, there was still a significant upward trend toward an increased mortality rate caused by the aging of the BC patients.
Our study provides novel insights on the epidemiological characteristics and longitudinal dynamics of BC in a fast urbanization and transitioning city. As a rare disease affecting all ages, the burden of BC among the elderly emerged to form an understudied and unmet medical need in an aging society.
Colonizing populations of alien invasive species are often unstable due to their small population size, ongoing gene flow, and ongoing adaptation to local conditions. These processes should lead to ...molecular signatures at the population level. However, temporal changes in genetic patterns after introduction are rarely examined. The western flower thrips,
Frankliniella occidentalis
(Pergande), is a globally invasive pest of vegetables and ornamental crops. Populations collected early in the invasion of China by this pest exhibited a strong population structure reflecting different invasion sources. Here, we re-examine this pattern after ten years. Over this period, genetic diversity has increased significantly, and the strong population genetic structure found in early sampling has declined. Gene flow between both geographically close and distant populations was identified. The loss of population structure likely reflects ongoing gene flow after colonization. Our results emphasize the importance of continuing to manage gene flow among invaded areas to limit the exchange of alleles that might facilitate further adaptive changes following a pest invasion.
► The article revealed FoxP3 gene function in gastric cancer firstly. ► Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. ► Overexpression ...of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. ► Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. ► FoxP3 is sufficient for activating the apoptotic signaling pathway.
Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.
Hyperglycemia is the dominant phenotype of diabetes and the main contributor of diabetic complications. Puerarin is widely used in cardiovascular diseases and diabetic vascular complications. ...However, little is known about its direct effects on diabetes. The aim of our study is to investigate its antidiabetic effect in vivo and in vitro, and explore the underlying mechanism. We used type I diabetic mice induced by streptozotocin to observe the effects of puerarin on glucose metabolism. In addition, oxidative stress and hepatic mitochondrial respiratory activity were evaluated in type I diabetic mice. In vitro, glucose consumption in HepG2 cells was assayed along with the qPCR detection of glucogenesis genes expression. Moreover, ATP production was examined and phosphorylation of AMPK was determined using Western blot. Finally, the molecular docking was performed to predict the potential interaction of puerarin with AMPK utilizing program LibDock of Discovery Studio 2018 software. The results showed that puerarin improved HepG2 glucose consumption and upregulated the glucogenesis related genes expression. Also, puerarin lowered fasting and fed blood glucose with improvement of glucose tolerance in type I diabetic mice. Further mechanism investigation showed that puerarin suppressed oxidative stress and improved hepatic mitochondrial respiratory function with enhancing ATP production and activating phosphorylation of AMPK. Docking study showed that puerarin interacted with AMPK activate site and enhancing phosphorylation. Taken together, these findings indicated that puerarin exhibited the hypoglycemic effect through attenuating oxidative stress and improving mitochondrial function via AMPK regulation, which may serve as a potential therapeutic option for diabetes treatment.
In this work, we design mesoporous silica-coated Prussian blue nanocubes with PEGyltation to construct multifunctional PB@mSiO2–PEG nanocubes. The PB@mSiO2–PEG nanocubes have good biocompatibility, ...excellent photothermal transformation capacity, in vivo magnetic resonance and photoacoustic imaging ability. After loading antitumor drug doxorubicin (DOX) in the PB@mSiO2–PEG nanocubes, the constructured PB@mSiO2–PEG/DOX nanoplatforms show an excellent pH-responsive drug release character within 48 h, namely, an ultralow cumulative drug release amount of 3.1% at pH 7.4 and a high release amount of 46.6% at pH 5.0. Upon near-infrared laser irradiation, the PB@mSiO2–PEG/DOX nanoplatforms show an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer than solo photothermal therapy or chemotherapy.
PDF
