Exo-miR-144-3p as a promising diagnostic biomarker for depressive symptoms in heart failure.

AIMS: The prevalence of depression is higher in heart failure (HF) patients. Early screening of depressive symptoms in HF patients and timely intervention can help to improve patients' quality of life and prognosis. This study aims to explore diagnostic biomarkers by examining the expression profile of serum exosomal miRNAs in HF patients with depressive symptoms. METHODS: Serum exosomal RNA was isolated and extracted from 6 HF patients with depressive symptoms (HF-DS) and 6 HF patients without depressive symptoms (HF-NDS). High-throughput sequencing was performed to obtain miRNA expression profiles and target genes were predicted for the screened differentially expressed miRNAs. Biological functions of the target genes were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, we collected serum exosomal RNAs from HF-DS (n = 20) and HF-NDS (n = 20). The differentially expressed miRNAs selected from the sequencing results were validated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Finally, the diagnostic efficacy of the differentially expressed exosomal miRNAs for HF-DS was evaluated by using receiver operating characteristic (ROC) curves. RESULTS: A total of 19 significantly differentially expressed exosomal miRNAs were screened by high-throughput sequencing, consisting of 12 up-regulated and 7 down-regulated exosomal miRNAs. RT-qPCR validation demonstrated that the expression level of exo-miR-144-3p was significantly down-regulated in the HF-DS group, and the expression levels of exo-miR-625-3p and exo-miR-7856-5p were significantly up-regulated. In addition, the expression level of exo-miR-144-3p was negatively correlated with the severity of depressive symptoms in HF patients, and that the area under the curve (AUC) of exo-miR-144-3p for diagnosing HF-DS was 0.763. CONCLUSIONS: In this study, we examined the serum exosomal miRNA expression profiles of HF patients with depressive symptoms and found that lower level of exo-miR-144-3p was associated with more severe depressive symptoms. Exo-miR-144-3p is a potential biomarker for the diagnosis of HF-DS.

Changes in carbohydrate distribution in cotton photosynthetic organs and increase in boll weight reduce yield loss under high temperature.

Yield of cotton (Gossypium hirsutum) does not always fall with high temperature (HT) even though this induces significant reductions in fruit retention. To investigate the underlying mechanisms, a greenhouse experiment was conducted with two temperature regimes [control treatment, 28 °C; high temperature (HT), 34 °C] for 7 d. Results showed HT did not significantly influence cotton yield, but reduced boll number and increased boll weight. The 13C distribution ratio of the leaf subtending the cotton boll (LSCB) decreased while that of the cotton boll increased under HT. Transcriptomic and proteomic analyses of the LSCB revealed up-regulated genes involved in cytokinin and jasmonic acid synthesis, as well as SWEET15 (GH_D01G0218), which positively regulated photosynthesis and transport photosynthate, ultimately leading to increased boll weight. After 7 d recovery from HT, the 13C distribution ratio of the LSCB increased while that of the cotton boll decreased. However, boll weight still increased, which was related to increased amylase and sucrose phosphate synthase activities and up-regulated sucrose transport genes in the main-stem leaf and capsule wall. Thus, both accelerated sucrose synthesis and transport in the LSCB under HT and increased sucrose supply ability of the main-stem leaf and capsule wall after recovery from HT contributed to an increased boll weight, which finally maintained cotton yield.

The role of CD38 in inflammation-induced depression-like behavior and the antidepressant effect of (R)-ketamine.

CD38 is involved in immune responses, cell proliferation, and has been identified in the brain, where it is implicated in inflammation processes and psychiatric disorders. We hypothesized that dysfunctional CD38 activity in the brain may contribute to the pathogenesis of depression. To investigate the underlying mechanisms, we used a lipopolysaccharide (LPS)-induced depression-like model and conducted behavioral tests, molecular and morphological methods, along with optogenetic techniques. We microinjected adeno-associated virus into the hippocampal CA3 region with stereotaxic instrumentation. Our results showed a marked increase in CD38 expression in both the hippocampus and cortex of LPS-treated mice. Additionally, pharmacological inhibition and genetic knockout of CD38 effectively alleviated neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, subsequently improving depression-like behaviors. Moreover, optogenetic activation of glutamatergic neurons of hippocampal CA3 reduced the susceptibility of mice to depression-like behaviors, accompanied by reduced CD38 expression. We also found that (R)-ketamine, which displayed antidepressant effects, was linked to its anti-inflammatory properties by suppressing increased CD38 expression and reversing synaptic defects. In conclusion, hippocampal CD38 is closely linked to depression-like behaviors in an inflammation model, highlighting its potential as a therapeutic target for antidepressant development.

Outdoor fine particulate matter exposure and telomere length in humans: A systematic review and meta-analysis.

Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 µg/m3 increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (ß) of -0.12 (95% CI: -0.20, -0.03, I2= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I2= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.

[Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway].

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-ß-galactosidase(SA-ß-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1ß(IL-1ß), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1ß and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1ß and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Deleterious effects of viral pneumonia on cardiovascular system.

Viral pneumonia has a significant effect on the cardiovascular system through various mechanisms; even though it is traditionally regarded as a pulmonary disease characterized by dyspnoea and hypoxaemia. Recent research works have shown that cardiovascular events outweigh all other causes of death in various influenza pandemics. Therefore, the exploration of the effects of viral pneumonia on cardiovascular system becomes increasingly essential. The objective of this review is three-fold: first, to summarize the knowledge about the epidemiological characteristics and clinical manifestations of viral infections that are the recent causes of global pandemics; second, to explore the cardiovascular response to these infections; and third, to attempt in identifying the possible coping strategies of the Wuhan epidemic and the future viral infection pandemics.

Nervous system involvement after infection with COVID-19 and other coronaviruses.

Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system.

Gut microbiota connects the brain and the heart: potential mechanisms and clinical implications.

Nowadays, high morbidity and mortality of cardiovascular diseases (CVDs) and high comorbidity rate of neuropsychiatric disorders contribute to global burden of health and economics. Consequently, a discipline concerning abnormal connections between the brain and the heart and the resulting disease states, known as psychocardiology, has garnered interest among researchers. However, identifying a common pathway that physicians can modulate remains a challenge. Gut microbiota, a constituent part of the human intestinal ecosystem, is likely involved in mutual mechanism CVDs and neuropsychiatric disorder share, which could be a potential target of interventions in psychocardiology. This review aimed to discuss complex interactions from the perspectives of microbial and intestinal dysfunction, behavioral factors, and pathophysiological changes and to present possible approaches to regulating gut microbiota, both of which are future directions in psychocardiology.

Copper-Induced In Vivo Gene Amplification in Budding Yeast.

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline-glutamate-serine-threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 µM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.

BSHXF-medicated serum combined with ADSCs regulates the TGF-ß1/Smad pathway to repair oxidatively damaged NPCs and its component analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lower back pain (LBP) is a common and frequent clinical condition, and intervertebral disc degeneration (IDD) is recognized as the leading cause of LBP, typically manifested by increased nucleus pulposus cell (NPC) senescence and death. In recent years, the treatment of IDD with stem cell injections has had great potential compared to surgical treatment. Combining the two may achieve better results, as BuShenHuoXueFang (BSHXF) is an herbal formula that improves the survival rate of transplanted stem cells and enhances their efficacy. AIM OF THE STUDY: We aimed to qualitatively and quantitatively analyze BSHXF-medicated serum and investigate the molecular mechanism of BSHXF-mediated serum in promoting the differentiation of adipose mesenchymal stem cells (ADSCs) into NPCs and delaying the senescence of NPCs by regulating the TGF-ß1/Smad pathway. MATERIALS AND METHODS: In this study, an ultrahigh-performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UPLC-Q-TOF-MS) was used to establish a method for the analysis of rat serum samples to track the active components in vivo; the oxidative damage model of NPCs was induced by T-BHP, and a Transwell chamber was used to construct a coculture system of ADSCs and NPCs. Flow cytometry was used to determine the cell cycle; SA-ß-Gal staining was used to assess cell senescence; ELISA was used to detect IL-1ß, IL-6 inflammatory factors, CXCL-1, CXCL-3, CXCL-10 chemokines, and TGF-ß1 in the supernatants of ADSCs and NPCs. WB was used to detect COL2A1, COL1A1, and Aggrecan in ADSCs to assess the manifestation of NP differentiation in ADSCs, and the WB method was used to detect COL2A1, COL1A1, Aggrecan, p16, p21, p53, and p-p53 protein expression in NPCs to reflect the cellular senescence status and to detect TGF-ß1, Smad2, Smad3, p- Smad2, and p- Smad3 protein expression in NPCs to reflect the pathway condition. RESULTS: We finally identified 70 blood components and their metabolites, including 38 prototypes, from the BSHXF-medicated serum. Compared with that in the nonmedicated serum group, the TGF-ß1/Smad pathway was activated in the medicated serum group, ADSCs moved toward NPC characteristics, the number of NPCs in the S/G2M phase increased, the number of senescent NPCs decreased, IL-1ß and IL-6 inflammatory factors in the Transwell decreased, CXCL-1, CXCL-3, and CXCL-10 chemokines decreased, and the expression of p16, p21, p53 and p-p53 proteins in NPCs was inhibited. CONCLUSION: By regulating the TGF-ß1/Smad pathway, BSHXF-medicated serum promoted ADSCs to NPCs, effectively alleviated the cycle blockage of NPCs after oxidative damage, encouraged the growth and proliferation of NPCs, delayed the aging of NPCs, improved the deteriorating microenvironment around NPCs, and repaired oxidatively damaged NPCs. The combination of BSHXF or its compounds with ADSCs has great potential for the treatment of IDD in the future.

A bibliometric analysis of research on heart failure comorbid with depression from 2002 to 2021.

Heart failure (HF) with depression is a common comorbidity associated with worse clinical status and quality of life. Although there have been numerous high-quality studies and relevant reviews on HF comorbid with depression, few bibliometric analyses of this field have been reported. In order to understand the development process, research hotspots and future directions, this review analyzes the papers on HF comorbid with depression from January 2002 to December 2021 through CiteSpace and VOSviewer. Visual cooperative networks between countries, authors and institutions were conducted to understand the basic development status of HF comorbid with depression. Furthermore, we performed co-occurrence analysis, burst detection, and timeline analysis for keywords to understand this field's research directions and hotspots. Finally, a detailed review and analysis of the classical literature in this field were conducted based on co-citation analysis. This bibliometric analysis provides an overview of studies on HF comorbid with depression and emphasizes the research on comorbidity mechanisms and more effective interventions as a priority for future research.

Identification and validation of ferroptosis-related genes and immune infiltration in ischemic cardiomyopathy.

Background: Cardiomyocyte death is an important pathophysiological basis for ischemic cardiomyopathy (ICM). Many studies have suggested that ferroptosis is a key link in the development of ICM. We performed bioinformatics analysis and experiment validation to explore the potential ferroptosis-related genes and immune infiltration of ICM. Methods: We downloaded the datasets of ICM from the Gene Expression Omnibus database and analyzed the ferroptosis-related differentially expressed genes (DEGs). Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein-protein interaction network were performed to analyze ferroptosis-related DEGs. Gene Set Enrichment Analysis was used to evaluate the gene enrichment signaling pathway of ferroptosis-related genes in ICM. Then, we explored the immune landscape of patients with ICM. Finally, the RNA expression of the top five ferroptosis-related DEGs was validated in blood samples from patients with ICM and healthy controls using qRT-PCR. Results: Overall, 42 ferroptosis-related DEGs (17 upregulated and 25 downregulated genes) were identified. Functional enrichment analysis indicated several enriched terms related to ferroptosis and the immune pathway. Immunological analysis suggested that the immune microenvironment in patients with ICM is altered. The immune checkpoint-related genes (PDCD1LG2, LAG3, and TIGIT) were overexpressed in ICM. The qRT-PCR results showed that the expression levels of IL6, JUN, STAT3, and ATM in patients with ICM and healthy controls were consistent with the bioinformatics analysis results from the mRNA microarray. Conclusion: Our study showed significant differences in ferroptosis-related genes and functional pathway between ICM patients and healthy controls. We also provided insight into the landscape of immune cells and the expression of immune checkpoints in patients with ICM. This study provides a new road for future investigation of the pathogenesis and treatment of ICM.

Landscape of gut microbiota and metabolites and their interaction in comorbid heart failure and depressive symptoms: a random forest analysis study.

IMPORTANCE: There is increasing evidence that alterations in gut microbial composition and function are associated with cardiovascular or psychiatric disease. Therefore, it is meaningful to investigate the taxonomic and functional characterization of the microbiota in HF patients who also have depressive symptoms. In this cross-sectional study, Cloacibacillus and alpha-tocopherol were determined as new diagnostic markers. Furthermore, intestinal microecosystem disorders are closely linked to depressive symptoms in HF patients, providing a new reference viewpoint for understanding the gut-heart/brain axis.

The effects of Jiawei Duhuo Jisheng mixture on Wnt/ß-catenin signaling pathway in the synovium inflamed by knee osteoarthritis: An in vitro and in vivo experiment.

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (KOA) is one of the common age-degenerative diseases. Recent studies have demonstrated that the pathogenesis of KOA is closely related to synovial lesions. Jiawei Duhuo Jisheng mixture (JDJM) has shown great potential in the treatment of KOA. However, the effect and mechanism of JDJM on synovial lesions of KOA remain unclear. AIM OF THE STUDY: The regulatory effect of JDJM on the Wnt/ß-catenin signaling pathway in KOA inflamed synovium was studied via in vitro and in vivo experiments, respectively. MATERIALS AND METHODS: For the in vitro experiment, fibroblasts were isolated from the rabbit synovium with KOA. The fibroblasts were grouped as follows: the vehicle group was given 0.5% FBS; the inhibitor group was treated with 0.5% volume fraction of XAV939; the normal serum groups and JDJM serum groups were treated with 5%, 10%, and 20% volume fractions of normal serum and JDJM-containing serum. The expression levels of Wnt3a, ß-catenin, Cyclin D1, metalloproteinase-7(MMP-7) and cyclooxygenase-2(COX-2) were detected by different assays 48 and 72 h after the intervention. For the in vivo experiment, the rabbit KOA model was prepared using the improved Hulth modeling method, whereby all rabbits were randomly divided into normal control, model control, positive control, and traditional Chinese medicine (TCM) groups. The expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 were detected by different assays in the 2, 4, and 8 weeks of treatment. RESULTS: In the two test results of in vitro experiments, the normal serum group was compared with the JDJM-containing serum group with the same volume fraction, demonstrating that mRNA transcription and protein expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7, and COX-2 in the latter decreased (P < 0.05), with more pronounced effects observed in the group treated with 20% volume fraction of JDJM serum. Compared with the inhibitor group, there was no significant difference (P > 0.05) in the mRNA transcription and protein expression levels, i.e., Wnt3a, ß-catenin, Cyclin D1, and MMP-7 were observed in the JDJM serum groups, except for a significant decrease (P < 0.05) in the level of mRNA transcription and protein expression of COX-2. Based on the in vivo experiment, compared to the model control group, articular cartilage, synovial hyperplasia, and the inflammatory reaction of the TCM group at different treatment times were significantly improved. The mRNA transcription level of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 detected by RT-qPCR and the protein expression level of Wnt3a, ß-catenin, Cyclin D1, MMP-7 and COX-2 detected by Western blot were significantly reduced (P < 0.05), and the effect was more evident at the eighth week. CONCLUSION: JDJM can regulate the synovial Wnt/ß-catenin signaling pathway in KOA models, reduce the mRNA transcription and protein expression levels of Wnt3a, ß-catenin, Cyclin D1, MMP-7, and COX-2 in the synovium, thus inhibiting synovial inflammation and protecting articular cartilage, which could be the key mechanism of action in treating this disease.

STAT4 and COL1A2 are potential diagnostic biomarkers and therapeutic targets for heart failure comorbided with depression.

BACKGROUND: Heart failure (HF) and depression are common disorders that markedly compromise quality of life and impose a great financial burden on the society. Although increasing evidence has supported the closely linkage between the two disorders, the comorbidity mechanisms remain to be fully illuminated. We performed a bioinformatics network analysis to understand potential diagnostic biomarkers and therapeutic targets for HF comorbided with depression. METHODS: We downloaded the datasets of HF and depression from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis (WGCNA) to identify key modules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the common genes existing in the HF and depression related modules. Then, we employed the STRING database to construct the protein-protein interaction (PPI) network and detected the hub genes in the network. Finally, we validated the expression difference of hub genes from additional datasets of HF and depression. RESULTS: Functional enrichment analysis indicated that platelet activation, chemokine signaling and focal adhesion were probably involved in HF comorbided with depression. PPI network construction indicated that HF comorbided with depression is likely related to 5 hub genes, including STAT4, CD83, CX3CR1, COL1A2, and SH2D1B. In validated datasets, STAT4 and COL1A2 were especially involved in the comorbidity of HF and depression. CONCLUSION: Our work indicated a total of 5 hub genes including STAT4, CD83, CX3CR1, COL1A2, and SH2D1B, in which STAT4 and COL1A2 especially underlie the comorbidity mechanisms of HF and depression. These shared pathways might provide new targets for further mechanistic studies of the pathogenesis and treatment of HF and depression.

Role of depressive symptoms in the prognosis of heart failure and its potential clinical predictors.

AIMS: This study aims to analyse the factors associated with prognosis in hospitalized patients with heart failure, particularly the role of depressive symptoms, and to develop a prediction model for depressive symptoms based on clinical characteristics in hospitalized patients with heart failure. METHODS AND RESULTS: Baseline information was collected at admission, and patients were followed up after discharge. The endpoint events were being hospitalized for heart failure or all-cause death. Depressive symptoms were evaluated and defined via the Patient Health Questionnaire (PHQ)-2 and PHQ-9. The bidirectional elimination was used to screen independent predictors of heart failure with depression symptoms. The least absolute shrinkage and selection operator (LASSO) optimized the predictor variables, and the prediction model was constructed. The model was internally validated by the bootstrap sampling method (Bootstrap), and its performance was assessed by discrimination and calibration. The mean age of patients with heart failure was 69.43 ± 12.15 years, and the proportion of males was 66.67%. The prevalence of depressive symptoms in hospitalized patients with heart failure was 46.83%, and the prevalence of moderate/severe depressive symptoms was 11.62%. Eighty cases (30.30%) were readmitted for heart failure, and 13 cases (4.92%) were all-cause deaths. Depressive symptoms (HR = 2.43, 95% CI: 1.55-3.80) and the PHQ-9 score (HR = 1.11, 95% CI: 1.06-1.16) were both independent risk factors for endpoint events (P < 0.001). For heart failure patients combined with depressive symptoms, obesity (OR = 0.27, 95% CI: 0.09-0.77, P = 0.015), N-terminal brain natriuretic peptide precursor (NT-proBNP) level (lnNT-proBNP: OR = 1.55, 95% CI: 1.20-2.01, P < 0.001) and red blood cell distribution width (RDW) (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004) were the independent factors. Six variables, including cardiovascular disease hospitalization history, obesity, renal insufficiency, NT-proBNP level, neutrophil ratio and RDW, were included to construct the prediction model. The area under the curve (AUC) was 0.730 in the original data, and the calibration curve was approximately distributed along the reference line in Bootstrap (500 resamplings), indicating the high level of discrimination and calibration of this model. CONCLUSIONS: Depressive symptoms and the PHQ-9 score are both independent risk factors for the prognosis of hospitalized patients with heart failure. In hospitalized patients with heart failure, the risk prediction model developed in this study has good predictive power for depressive symptoms.

An Alternatively Spliced p62 Isoform Confers Resistance to Chemotherapy in Breast Cancer.

Resistance to chemotherapy remains a major obstacle to the successful treatment of breast cancer. More than 80% of patients who receive neoadjuvant chemotherapy (NAC) do not achieve a pathologic complete response. In this study, we report a novel p62 mRNA isoform with a short 3'-UTR (untranslated region; p62-SU, 662-nt) that is associated with chemoresistance in breast cancer cells and tissue specimens. The p62 mRNA isoform was identified by RNA sequencing with qRT-PCR, 3'-RACE, and Northern blot analysis. In vitro and in vivo, ectopic expression of p62-SU promoted breast cancer cell proliferation, migration, invasion, and chemoresistance compared with the p62 mRNA isoform with a full-length 3'-UTR (p62-LU, 1,485-nt). Mechanistically, cleavage and polyadenylation specific factor 1 (CPSF1) modulated the 3'-UTR of p62 through alternative polyadenylation. In addition, p62-SU escaped miR-124-3p-mediated repression and upregulated p62-SU protein expression, thereby inducing p62-dependent chemoresistance. These data suggest that a CPSF1-p62-miR-124-3p signaling axis is responsible for reduced sensitivity of breast cancer to chemotherapy. SIGNIFICANCE: Resistance to NAC in breast cancer is driven by a novel p62 mRNA isoform that escapes miRNA-mediated repression and leads to increased p62 protein expression.

New Insights Into the Comorbidity of Coronary Heart Disease and Depression.

Coronary heart disease (CHD) and depression are common disorders that markedly impair quality of life and impose a great financial burden on society. They are also frequently comorbid, exacerbating patient condition, and worsening prognosis. This comorbidity strongly suggests shared pathologic mechanisms. This review focuses on the incidence of depression in patients with CHD, deleterious effects of depression on CHD symptoms, and the potential mechanisms underlying comorbidity. In addition to the existing frequent mechanisms that are well known for decades, this review summarized interesting and original potential mechanisms to underlie the comorbidity, such as endocrine substances, gut microbiome, and microRNA. Finally, there are several treatment strategies for the comorbidity, involving drugs and psychotherapy, which may provide a theoretical basis for further basic research and clinical investigations on improved therapeutic interventions.

Serum Levels of FGF21, ß-Klotho, and BDNF in Stable Coronary Artery Disease Patients With Depressive Symptoms: A Cross-Sectional Single-Center Study.

Background: The incidence of depressive symptoms (DS) in patients with stable coronary artery disease (SCAD) is significantly higher than those in healthy population, and that DS are independent risk factors for cardiovascular events. Previous studies have reported that fibroblast growth factor 21 (FGF21), ß-klotho, mature brain-derived neurotrophic factor (mBDNF), and BDNF precursor (proBDNF) play important roles in the pathogenesis and treatment of coronary heart disease and depression. With this in mind, the present study aimed to clarify the relationship between FGF21, ß-klotho, mBDNF, and proBDNF and SCAD with comorbid depression, in addition to also exploring the underlying mechanisms of these disease processes. Methods: A total of 116 patients with SCAD and 45 healthy controls were recruited. Patients with SCAD were further divided into two subgroups based on the Zung Self-Rating Depression Scale (SDS), which were characterized as those with no DS (NDS) and those with DS. Baseline data were collected, and serum levels of FGF21, ß-klotho, mBDNF, and proBDNF were determined. Results: In SCAD patients, Gensini scores-denoting the degree of coronary arteriostenosis-were significantly greater in the DS group than in the NDS group. There was also a positive correlation between the Gensini scores and the SDS scores. Patients in the SCAD group demonstrated a lower serum FGF21. Serum ß-klotho, mBDNF, and mBDNF/proBDNF were also significantly lower in the DS group than in the NDS group. Furthermore, ß-klotho and mBDNF were negatively correlated with the SDS scores. Additionally, SCAD patients were divided into lower- and higher-level groups using hierarchical cluster analysis, with the results highlighting that patients in the lower mBDNF group had a higher incidence of DS. Conclusions: The depression score was positively correlated with the severity of coronary artery stenosis, and serum FGF21, ß-klotho, mBDNF, and proBDNF were closely related to the development of DS in patients with SCAD. These observations suggest FGF21, ß-klotho, mBDNF, and proBDNF as potential diagnostic and/or therapeutic targets for SCAD with co-morbid depression.