The impact of social support on benefit finding among patients with advanced lung cancer and their caregivers: based on actor-partner interdependence mediation model.

PURPOSE: Advanced lung cancer and its treatment serve as a sudden stressful event that profoundly impacts the psychological experience of both the patients and their primary caregiver. This study used dyadic analyses to explore the dyadic effects of social support on benefit finding and whether hope level mediates the patient-caregiver dyads in advanced lung cancer. METHODS: Two hundred ninety-five pairs of patients with advanced lung cancer and primary caregivers completed the Social Support Rating Scale (SSRS), the Herth Hope Index (HHI), and the Benefit Finding Scale (BFS). Dyadic analyses were conducted using structural equation modelling based on the actor-partner interdependence mediation model. RESULTS: The results indicated that for both patients (B = 0.259, 95% CI = 0.135-0.423, P < 0.001) and their primary caregivers (B = 0.596, 95% CI = 0.403-0.838, P < 0.001), hope level mediated the actor effect of social support on benefit finding; social support was positively associated with hope level and further enhanced benefit finding. Regarding partner effects (B = 0.242, 95% CI = 0.119-0.404, P < 0.001), primary caregivers' social support significantly indirectly affected patients' benefit finding through patients' hope level. CONCLUSION: There is an interaction between social support, hope level, and benefit finding in patients with advanced lung cancer and their primary caregivers. Healthcare professionals ought to be vigilant in recognizing patients and caregivers who are vulnerable, have limited social support, and possess diminished hope levels. At the same time, nurses should provide timely psychological support and counseling to patients and their caregivers, encourage them to actively participate in social activities, and inspire their confidence and hope in life, thus improving their benefit findings.

Lactobacillus acidophilus and HKL Suspension Alleviates Ulcerative Colitis in Rats by Regulating Gut Microbiota, Suppressing TLR9, and Promoting Metabolism.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with complex pathogenesis. The intestinal flora disturbance affects the homeostasis of the intestinal environment, leading to metabolic imbalance and immune abnormalities of the host, contributing to the perpetuation of intestinal inflammation. We suggest that the combination of anti-inflammatory therapy and the regulation of intestinal flora balance may help in the treatment process. Previously, we used a combination treatment consisting of Lactobacillus acidophilus (Lac) and Chinese medicine Huan Kui Le (HKL) suspension in a UC rat model, where the combined intervention was more effective than either treatment alone. Herein, the mechanism of action of this combined treatment has been investigated using 16S rRNA sequencing, immunohistochemistry, and ELISA methods in the colon, and untargeted metabolomics profiling in serum. Colon protein expression levels of IL-13 and TGF-ß were upregulated, whereas those of TLR9 and TLR4 were downregulated, consistent with an anti-inflammatory effect. In addition, gut microbiota structure changed, shown by a decrease in opportunistic pathogens correlated with intestinal inflammation, such as Klebsiella and Escherichia-Shigella, and an increase in beneficial bacteria such as Bifidobacterium. The latter correlated positively with IL-13 and TGF-ß and negatively with IFN-γ. Finally, this treatment alleviated the disruption of the metabolic profile observed in UC rats by increasing short-chain fatty acid (SCFA)-producing bacteria in the colonic epithelium. This combination treatment also affected the metabolism of lactic acid, creatine, and glycine and inhibited the growth of Klebsiella. Overall, we suggest that treatment combining probiotics and traditional Chinese medicine is a novel strategy beneficial in UC that acts by modulating gut microbiota and its metabolites, TLR9, and cytokines in different pathways.

The Antitumor Effect and Mechanism of Total Flavonoids From Coreopsis Tinctoria Nutt (Snow Chrysanthemum) on Lung Cancer Using Network Pharmacology and Molecular Docking.

Coreopsis tinctoria Nutt (C. tinctoria), also known as Snow Chrysanthemum, is rich in polyphenols and flavonoids. It has important pharmacological effects such as lowering blood lipids, regulating blood glucose, and anti-tumor effect. However, its anti-tumor mechanism has not yet been investigated thoroughly. This study aimed to explore the anti-tumor effect of total flavonoids extracted from C. tinctoria (CTFs) on lung cancer and the possible mechanism. The components of CTFs were analyzed using Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The active components of CTFs were screened according to oral bioavailability (OB) and drug-likeness (DL). Totally, 68 components of CTFs were identified and 23 active components were screened. Network pharmacological analysis on the active components identified 288 potential targets associated with lung cancer. After protein-protein interaction (PPI) network topology analysis, 17 key protein targets including Akt1, MAPK1, TP53, Bcl-2, Caspase-3, Bax, GSK3B and CCND1 were screened. The molecular docking results showed that the active components of CTFs had good binding activity with key targets. GO and KEGG analysis of candidate targets found that the main enrichment was in PI3K/Akt-mediated intrinsic apoptotic pathways. Finally, according to the results of network pharmacology, the potential molecular mechanism of CTFs intervention in lung cancer was validated experimentally in vitro and in vivo. The experimental validation results demonstrated that the antitumor activity of CTFs on lung cancer may be related to inhibiting the PI3K-Akt signaling pathway and activating the mitochondrial-mediated apoptosis pathway.

ACSM3 suppresses the pathogenesis of high-grade serous ovarian carcinoma via promoting AMPK activity.

PURPOSE: Ovarian carcinoma is the fifth commonest malignancy in females and exhibits a high recurrence rate. High-grade serous ovarian carcinoma (HGSOC) is the main histologic subtype. It displays extensive genetic heterogeneity. Here, we aimed to identify potential therapeutic targets for HGSOC. METHODS: Both bioinformatic data from TCGA and 73 pairs of tumor and normal samples from patients were analyzed to reveal the expression level of ACSM3 in HGSOC. Next, cellular and animal experiments, including cell proliferation, colony formation and xenograft assays were performed to explore the suppressive function of ACSM3. Finally, biochemical methods, AMP/ATP ratio measurements and Western blotting were used to elucidate the mechanism underlying the ACSM3-AMPK axis in HGSOC. RESULTS: After analyzing transcriptome data of TCGA HGSOC samples, we found that ACSM3 is down-regulated in patient samples compared with normal controls. This observation was validated using data from primary clinical samples. Proliferation, soft agar colony formation and xenograft assays revealed that ACSM3 is able to suppress HGSOC tumor growth both in vitro and in vivo. Moreover, we found that ACSM3 overexpression increased the AMP/ATP ratio and the phosphorylation level of AMPK at threonine 172. In addition, we found that AMPK silencing in EFO21 and SKOV3 cells completely abolished the anti-oncogenic effect of ACSM3. CONCLUSION: Our data indicate that the ACSM3-AMPK axis is involved in the pathogenesis of HGSOC and, as such, may act as a therapeutic target for this cancer.

Electrochemical sulfonylation of enamides with sodium sulfinates to access ß-amidovinyl sulfones.

The electrochemical sulfonylation of enamides with sodium sulfinates was developed in an undivided cell in constant current mode, leading to the formation of ß-amidovinyl sulfones in moderate to good yields. The catalyst-, electrolyte- and oxidant-free protocol features good functional group tolerance and employs electric current as a green oxidant. Mechanistic insights into the reaction indicate that the reaction may proceed via a radical mechanism.

Elevated LINC00909 Promotes Tumor Progression of Ovarian Cancer via Regulating the miR-23b-3p/MRC2 Axis.

Ovarian cancer (OC), the third common gynecologic malignancy, contributes to the most cancer-caused mortality in women. However, 70% of patients with OC are diagnosed at an advanced stage, of which the 5-year survival is less than 30%. Long noncoding RNAs (long ncRNAs or lncRNA), a type of RNA with exceeding 200 nucleotides in length but no protein-coding capability, have been demonstrated to involve the pathogenesis of various cancers and show considerable potential in the diagnosis of OC. In this study, we found that the LINC00909 expression in tumor and serum specimens of OC patients was elevated, determined by real-time quantitative, and droplet digital PCR. In receiver operating characteristic (ROC) analysis, our results revealed that serum LINC00909 distinguished cancers from normal ovarian tissue with 87.8% of sensitivity and 69.6% of specificity (AUC, 81.2%) and distinguished serous ovarian cancer from normal ovarian tissue with 90.0% of sensitivity and 75.9% of specificity (AUC, 84.5%). Furthermore, we observed that the tumor and serum LINC00909 level was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and the Eastern Cooperative Oncology Group (ECOG) score (reflecting patients' performance status). Also, patients with low serum LINC00909 level showed a longer overall (hazard ratio, HR = 1.874, p = 0.0004) and progression-free (HR = 1.656, p = 0.0017) survival. Functional assays indicated that the elevation of LINC00909 expression contributes to cell proliferation, migration, and invasion capability of ovarian cancer cells. Besides, we demonstrated that LINC00909 functions as a competing endogenous RNA (ceRNA) of MRC2 mRNA by sponging miR-23-3p, and thereby promotes epithelial-to-mesenchymal transition (EMT) of ovarian cancer cells. Therefore, we highlight that the LINC00909/miR-23b-3p/MRC2 axis is implicated in the pathogenesis of ovarian cancer, and serum LINC00909 may be a promising biomarker for the diagnosis of OC.

Value of refined care in patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Under physiological conditions, sputum produced during acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can move passively with the cilia in the airway; the sputum is gradually excreted from the depth of the airways through the stimulation of the coughing reflex on the sensory nerve on the surface of the airway. However, when the sputum is thick, the cough is weak, or the tracheal cilia are abnormal, sputum accumulation may occur and affect the exchange of oxygen and carbon dioxide in the lung. Furthermore, the presence of pathogenic microorganisms in sputum may cause or aggravate the symptoms of pulmonary infection in patients, which is the main factor leading to AECOPD. Therefore, promoting effective drainage of sputum and maintaining airway opening are key points requiring clinical attention. AIM: To explore the effect of refined nursing strategies in patients with AECOPD and dysphagia. METHODS: We selected 126 patients with AECOPD and difficulty of expectoration at our hospital, and divided them into a refined care group and a routine care group, with 63 cases each, using a random number table. The two groups of patients were treated with expectorant, anti-infection, oxygen inhalation, and other basic treatment measures; patients in the refined care group were given refined nursing intervention during hospitalization, and the routine care group received conventional nursing intervention. The differences in sputum expectoration, negative pressure suction rate, blood gas parameters, dyspnea score measured through the tool developed by the Medical Research Council (MRC), and quality of life were compared between the two groups. RESULTS: After 7 d of intervention, the sputum expectoration effect of the refined care group was 62.30%, the effective rate was 31.15%, and the inefficiency rate was 6.56%. The sputum expectoration effect of the routine care group was 44.07%, the effective rate was 42.37%, and the inefficiency rate was 13.56%. The refined care group had better sputum expectoration than the routine care group (P < 0.05). The negative pressure suction rate in the refined care group was significantly lower than that of the routine care group during the treatment (22.95% vs 44.07%, P < 0.05). Before the intervention, the arterial oxygen saturation (PaO2) and arterial carbon dioxide saturation (PaCO2) values were not significantly different between the two groups (P > 0.05); the PaO2 and PaCO2 values in the refined care group were comparable to those in the routine care group after 7 d of intervention (P > 0.05). Before the intervention, there was no significant difference in the MRC score between the two groups (P > 0.05); the MRC score of the refined care group was lower than that of the routine care group after 7 d of intervention, but the difference was not statistically significant (P > 0.05). Before intervention, there was no significant difference in the symptoms, activities, disease impact, or St. George's Respiratory questionnaire (SGRQ) total scores between the two groups (P > 0.05). After 7 days of intervention, the symptoms, activities, and total score of SGRQ of the refined care group were higher than those of the routine care group, but the difference was not statistically significant (P > 0.05). CONCLUSION: AECOPD with thick sputum, weak coughing reflex, and abnormal tracheal cilia function will lead to sputum accumulation and affect the exchange of oxygen and carbon dioxide in the lung. Patients with AECOPD who have difficulty expectorating sputum may undergo refined nursing strategies that will promote expectoration, alleviate clinical symptoms, and improve the quality of life.

Effect of HMGN2 on proliferation and apoptosis of MCF-7 breast cancer cells.

We investigated the effect of high mobility group protein N2 (HMGN2) on the proliferation and apoptosis of the human MCF-7 breast cancer cell line, and its effect on tumor growth in a subcutaneous heterotopic transplantation tumor model of breast cancer. The cell viability assay was used to verify the effect of the recombinant human HMGN2 on MCF-7 cell proliferation. The Transwell chamber assay was used to verify the effect of HMGN2 on MCF-7 cell migration. Flow cytometry and Hoechst staining were used to detect the effect of HMGN2 on MCF-7 cell apoptosis. MCF-7 was injected to establish a subcutaneous heterotopic transplantation tumor model of breast cancer in nude mice. The size, weight and volume of tumor in each group were compared after the administration of different concentrations of HMGN2 solution around the tumor tissue at day 1, 3, 5 and 7. The tumor tissue was removed and cut into sections, and the apoptotic cells in tumors of nude mice were detected by a TUNEL kit. The CCK-8 assay showed that HMGN2 at different concentrations inhibited the proliferation of the MCF-7 breast cancer cells, and the proliferation of MCF-7 cells were significantly inhibited when the concentration of HMGN2 reached 3 µg/ml (P<0.01). The Transwell chamber assay showed that 3 µg/ml of HMGN2 significantly decreased the migration capacity of MCF-7 cells (P<0.01). Flow cytometry and Hoechst staining showed that 3 µg/ml of HMGN2 significantly increased apoptosis of MCF-7 cells (P<0.01). After the nude mouse model of breast cancer was established, HMGN2 at different concentrations was injected around the tumor tissue at day 1, 3, 5 and 7. We demonstrated that the growth of breast cancer was significantly inhibited when the concentration of HMGN2 reached 15 µg/ml. TUNEL staining showed that the number of apoptotic cells in the 15 µg/ml dose group was significantly higher than that in the control group (P<0.01). Therefore, in vitro and in vivo experiments proved that recombinant human HMGN2 could significantly inhibit the proliferation and migration of breast cancer cells, which increased the apoptosis of breast cancer cells and exerted anti-breast cancer effects, which enriched our understanding of the biological roles of HMGN2.

Thyroid Dysfunction, Neurological Disorder and Immunosuppression as the Consequences of Long-term Combined Stress.

Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. So far, the molecular mechanisms of response to stressors still remain elusive. In the current study, after 10 days of repeated chronic stress (hot-dry environment and electric foot-shock), a murine model of combined-stress (CS) was created in the SPF Wistar rats. Meanwhile, we established an ulcerative-colitis (UC) rat model induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS)/ethanol enema according to previous studies. The blood, hypothalamus, and colon tissues of these rats from CS, normal control (NC), UC and sham (SH) groups, were collected for further investigations. Comparing to the NC group, the serum levels of T3, T4, fT3 and fT4 were obviously decreased in the CS group after chronic stress, indicating that thyroid dysfunction was induced by long-term combined stress. Moreover, the application of RNA-seq and subsequent analyses revealed that neurological disorder and immunosuppression were also caused in the hypothalamus and colon tissues, respectively. Comparing with SH group, besides the induced colon inflammation, thyroid dysfuntion and neurological disorder were also produced in the UC group, suggesting that hypothalamic-pituitary-thyroid (HPT) axis and gastrointestinal system might not function in isolation, but rather, have intricate crosstalks.

Liposome encapsulated luteolin showed enhanced antitumor efficacy to colorectal carcinoma.

Luteolin is a falconoid compound that is present in various types of plants and possesses remarkable potential as a chemopreventive agent. However, the poor aqueous solubility of luteolin limits its clinical application. In the present study, an approach towards chemoprevention was explored using liposomes to deliver luteolin, and the antitumor efficacy was investigated in colorectal carcinoma. The present findings demonstrated that luteolin was efficiently encapsulated into liposomes with an encapsulation efficiency as high as 90%. The particle size of the liposomal luteolin (Lipo­Lut) and ζ­potential were optimized. In vitro studies demonstrated that, Lipo­Lut had a significant inhibitory effect on the growth on the CT26 colorectal carcinoma cell line compared with free luteolin (Free­Lut). The in vivo study indicated that Lipo­Lut could achieve superior antitumor effects against CT26 tumor compared with luteolin alone. The present results suggested that liposome delivery of luteolin improved solubility, bioavailability and may have potential applications in chemoprevention in clinical settings.

[Metabonomic analysis of the urine from rat model with abnormal sapra syndrome].

OBJECTIVE: To investigate the correlation between the change in metabolic components of urine and the abnormal sapra syndrome by using a rat model of abnormal sapra syndrome.
 Methods: Multiple factors, such as dry environment, dry feed, and chronic electrical stimulation, were used to establish the abnormal sapra syndrome in Wistar rats by Uyghur medicine. The differences in metabolites were detected through the metabonomics method.
 Results: The urine of rats in abnormal sapra syndrome group showed significant high abundance metabolites as follows: Leucine, isoleucine, and glycoprotein. And that significant low abundance metabolites as follows: Glutamine, creatine, citric acid, and phenylalanine.
 Conclusion: The urine of rats with the abnormal sapra syndrome displays abnormal energy metabolism. It is likely that the dysfunctional metabolisms of three major nutrients might be the molecular basis for the abnormal sapra syndrome.

Abundance and diversity based on amoA genes of ammonia-oxidizing archaea and bacteria in ten wastewater treatment systems.

The abundance and diversity of amoA genes of ammonia-oxidizing archaea (AOA) and bacteria (AOB) were investigated in ten wastewater treatment systems (WTSs) by polymerase chain reaction (PCR), cloning, sequencing, and quantitative real-time PCR (qPCR). The ten WTSs included four full-scale municipal WTSs, three full-scale industrial WTSs, and three lab-scale WTSs. AOB were present in all the WTSs, whereas AOA were detected in nine WTSs. QPCR data showed that AOB amoA genes (4.625 × 10(4)-9.99 × 10(9) copies g(-1) sludge) outnumbered AOA amoA genes (

Quantitative analyses of the composition and abundance of ammonia-oxidizing archaea and ammonia-oxidizing bacteria in eight full-scale biological wastewater treatment plants.

This study investigated the diversity and abundance of AOA and AOB amoA genes in eight full-scale wastewater treatment plants (WWTPs). Although the process principles and system operations of the eight WWTPs were different, quantitative real-time PCR measurements showed that AOB amoA genes outnumbered AOA amoA genes with the ratio varying from 2.56 to 2.41×10(3), and ammonia may be partially oxidized by AOA. Phylogenetic analyses based on cloning and sequencing showed that Nitrososphaera cluster was the most dominant AOA species and might be distributed worldwide, and Nitrosopumilis cluster was few. Statistical analysis indicated that there might be versatile AOA ecotypes and some AOA might be not obligate autotrophic. The Nitrosomonas europaea cluster and Nitrosomonas oligotropha cluster were the two most dominant AOB species, and AOB species showed higher diversity than AOA species.

The chromosomal protein HMGN2 mediates the LPS-induced expression of ß-defensins in mice.

Human ß-defensin-2 (HBD-2), an antimicrobial peptide produced by epithelial cells, plays an important role in the body's innate and adaptive immunity. High-mobility group N2 (HMGN2), a member of the HMG superfamily, binds to chromatin to modulate gene transcription. Previously, we have shown that HMGN2 acts as a positive modulator of the signal transduction cascade in the process of inducible human ß-defensin expression. In our current study, we found that down-regulation of HMGN2 reduces the expression level of murine ß-defensin-3 and -4 (mBD-3 and mBD-4), but not mBD-1 upon LPS stimulation in various tissues of pregnant ICR mice, as well as in embryonic and neonatal lungs and livers at different developmental time points. In the control group, murine HMGN2 expression decreased, while mBD-1 and mBD-4 expression increased slightly during development. In the LPS-treated groups, murine HMGN2 and mBD-1 expression did not change significantly, whereas mBD-3 and mBD-4 expression significantly increased in maternal, embryonic, and neonatal tissues, especially the mBD-3 expression. HMGN2 shRNA interference led to decreased mBD-3 and mBD-4 expression, while mBD-1 expression did not significantly change. These results demonstrate that HMGN2 is a component of the LPS-induced mouse ß-defensin response.

High mobility group nucleosomal binding domain 2 protein protects bladder epithelial cells from Klebsiella pneumoniae invasion.

Due to the predominance of multiple-antibiotic-resistant Klebsiella pneumoniae strains, the search for new approaches for the prevention of K. pneumoniae infections is now under intensive investigation. The objective of the present study was to investigate the effects of high mobility group nucleosomal binding domain 2 (HMGN2) protein, which acts on the bladder epithelial cells T 24, on the invasion of K. pneumoniae 03183 and explore its possible mechanisms. Pretreatment with HMGN2 significantly reduced K. pneumoniae 03183 uptake by T 24 cells. In T 24 cells, there were no detectable cytotoxic effects of HMGN2 at any concentration between 32 and 256 µg/ml after 2 h incubation. HMGN2 exhibited no appreciable antibacterial activity against K. pneumoniae 03183. Fluorescence microscopy and flow cytometry analysis revealed that HMGN2 blocked K. pneumoniae 03183-induced actin polymerization. K. pneumoniae 03183-induced phosphorylation of extracellular signal-regulated kinase (ERK) and cofilin were prevented by pretreatment with HMGN2. These results indicated that pretreatment with HMGN2 inhibited cofilin phosphorylation and then induced actin disruption which may block ERK phosphorylation. These changes led to inhibition of K. pneumoniae 03183 invasion of T 24 bladder epithelial cells.

High-mobility group protein N2 (HMGN2) inhibited the internalization of Klebsiella pneumoniae into cultured bladder epithelial cells.

Since bacterial invasion into host cells is an important step in the infection process, using the agents to interfere with bacterial internalization is an attractive approach to block the infection process. In this work, we describe a new, previously unrecognized role of the human cationic host defense peptide HMGN2 during Klebsiella pneumoniae infections. Our results revealed that the internalization of K. pneumoniae strain 03183 into cultured bladder epithelial cells (T24) was significantly reduced at HMGN2 concentrations that were unable to produce any bacteriostatic or bactericidal effect. Using microarrays and follow-up studies, we demonstrated that HMGN2 affected the internalization of K. pneumoniae strain 03183 by inhibiting the attachment of bacteria, and then decreasing bacteria-induced ERK1/2 activation and actin polymerization, which might contribute to bacterial internalization into T24 cells. This disruption of bacterial internalization implied that HMGN2 could provide protection against K. pneumoniae infections.

The chromosomal protein HMGN2 mediates lipopolysaccharide-induced expression of ß-defensins in A549 cells.

Human ß-defensin-2 (HBD-2) is an antimicrobial peptide produced by the epithelial cells that plays an important role in innate and adaptive immunity. Here we report that high mobility group protein N2 (HMGN2), a member of the high mobility group superfamily that affects chromatin function, modulates the expression of HBD-2 in A549 cells treated by lipopolysaccharide. Mechanistically, HMGN2 prolongs the retention time and enhances the accumulation of nuclear factor κB p65 in the nucleus, and promotes the acetylation of p65 through increasing histone acetyltransferase activity and enhancing p65-Ser536 phosphorylation. Additionally, chromatin immunoprecipitation reveals that HMGN2 and p65 synergistically promote their specific binding to HBD-2 promoter, thereby affecting the downstream transcription. Taken together, these results suggest that HMGN2 acts as a positive modulator of nuclear factor κB signalling to promote lipopolysaccharide-induced ß-defensin expression.