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The global morbidity and mortality of colorectal cancer (CRC) are ranked the third among gastrointestinal tumors in the world. MiR-451a is associated with several types of cancer, including CRC. However, the roles and mechanisms of miR-451a in CRC have not been elucidated. BAP31 is a predicted target gene of miR-451a in our suppression subtractive hybridization library. Its relationship with miR-451a and function in CRC are unclear. We hypothesized that miR-451a could induce apoptosis through suppressing BAP31 in CRC. Immunohistochemistry and real-time PCR were used to measure BAP31 expressions in CRC tissues and pericarcinous tissues from 57 CRC patients and CRC cell lines. Dual-luciferase reporter assay was used to detect the binding of miR-451a to BAP31. The expression of BAP31 protein in CRC tissues was significantly higher than that in pericarcinous tissues, which was correlated with distant metastasis and advanced clinical stages of CRC patients. The expression of BAP31 was higher in HCT116, HT29, SW620, and DLD cells than that in the normal colonic epithelial cell line NCM460. The expression of BAP31 was absolutely down-regulated when over-expressing miR-451a in HCT116 and SW620 cells compared with control cells. Mir-451a inhibited the expression of BAP31 by binding to its 5’-UTR. Over-expressing miR-451a or silencing BAP31 suppressed the proliferation and apoptosis of CRC cells by increasing the expressions of endoplasmic reticulum stress (ERS)-associated proteins, including GRP78/BIP, BAX, and PERK/elF2α/ATF4/CHOP, which resulted in increased ERS, cytoplasmic calcium ion flowing, and apoptosis of CRC cells. These changes resulting from over-expressing miR-451a were reversed by over-expressing BAP31 with mutated miR-451a-binding sites. Over-expressing miR-451a or silencing BAP31 inhibited tumor growth by inducing ERS. The present study demonstrated that miR-451a can inhibit proliferation and increase apoptosis through inducing ERS by binding to the 5’-UTR of BAP31 in CRC.

(1) Background: Atopic dermatitis (AD) is characterized as a chronic inflammatory skin disease with a significant incidence rate. The pathophysiological mechanisms underlying AD remain incompletely understood. However, extensive research demonstrates that a complex interplay among genetic, immune, and environmental factors contributes to the disruption of skin barrier function. Inflammation is identified as one of the pathological mechanisms in AD. Recombined mussel adhesive protein exhibits anti-inflammatory properties. However, recombinant mussel adhesive protein has been used less frequently for AD, so we explored the therapeutic effect of recombinant mussel adhesive protein for AD and the potential mechanism. (2) Methods: We established a mice model of AD in vivo and an LPS-induced inflammation model in HaCaT cells in vitro. Through assessment of skin lesion scores, itch frequency, transepidermal water loss, skin microcirculation, HE staining, Elisa assays for IL-6, IL-12, IL-13, IL-4, IL-5, IFN-γ, IgE, and TNF-α, immunohistochemical staining for filaggrin and CK14, Masson staining, and Western blot analysis of NF-κB p65, P-P65, Keap1, and Nrf2, the effects of recombined mussel adhesive protein on AD symptoms, pathology, inflammation, and its mechanisms are investigated. (3) Results: The recombined mussel adhesive protein significantly improved the compromised skin barrier, reduced scratching frequency in mice, decreased transepidermal water loss, and lowered the expression of inflammatory factors, thus ameliorating skin inflammation damage. Mechanistically, recombined mussel adhesive protein downregulated the expression of P-p65/p65 and Keap1 while upregulating the level of Nrf2. (4) Conclusions: Overall, our results demonstrate the effectiveness of recombined mussel adhesive protein in attenuating DNFB-induced AD by inhibiting NF-κB and activating the Keap1/Nrf2 signaling pathway. Thus, recombined mussel adhesive protein is a promising therapeutic candidate for the treatment of AD.

Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF‐β1. RACK1 is the downstream target gene of TGF‐β1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS‐2B cells were cultured and exposed to recombinant soluble human TGF‐β1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA‐challenged mice, as well as TGF‐β1‐induced apoptosis and EMT of BEAS‐2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF‐β1 up‐regulated EMT related protein levels (N‐cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF‐β1‐induced N‐cadherin and Snail up‐regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF‐β1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF‐β1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

Ferroptosis is associated with multiple pathophysiological processes. Inhibition of ferroptosis has received much concern for some diseases. Nonetheless, there is no study comprehensively illustrating functions of ferroptosis-related genes (FRGs) in psoriasis. In this study, FRGs together with psoriasis-associated data were obtained in Ferroptosis Database (FerrDb) and gene expression omnibus (GEO) database separately. This work identified altogether 199 psoriasis-associated DE-FRGs, and they were tightly associated with immunity and autophagy modulation. Thereafter, the present study utilized SVM-RFE and LASSO algorithms to identify NR5A2, CISD1, GCLC, PRKAA2, TRIB2, ABCC5, ACSF2, TIMM9, DCAF7, PEBP1, and MDM2 from those 199 DE-FRGs to be marker genes. As revealed by later functional annotation, the marker genes possibly had important effects on psoriasis through being involved in diverse psoriasis pathogenesis-related pathways such as cell cycle, toll-like receptor (TLR), chemokine, and nod-like receptor (NLR) pathways. Moreover, altogether 37 drugs that targeted 11 marker genes were acquired. Besides, based on CIBERSORT analysis, alterations of immune microenvironment in psoriasis cases were possibly associated with PRKAA2, PEBP1, CISD1, and ACSF2. Taken together, this work established the diagnostic potency and shed more lights on psoriasis-related mechanism. More investigations are warranted to validate its value in diagnosing psoriasis before it is applied in clinic.

Background: Psoriasis represents the chronic, recurrent and inflammatory disorder. The Traditional Chinese Medicine Xiyanping injection (XYP) is extensively applied in China for treating diverse inflammatory disorders, such as bronchitis, viral pneumonia or upper respiratory tract infection. XYP may offer a potential treatment for psoriasis vulgaris (PV). This study focused on analyzing whether XYP combined with acitretin was effective and safe. Methods: The present meta-analysis was carried out in line with guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic review was registered in PROSPERO (CRD42022333273). Besides, relevant randomized controlled trials (RCTs) that compared XYP plus acitretin with acitretin alone for treating PV were searched from several databases from their inception till May 2022. In addition, this work utilized RevMan5.4 to conduct risk assessment as well as meta-analysis. Results: This meta-analysis selected altogether 10 RCTs including 815 subjects. Upon quality assessment, the RCTs mainly had low or unclear risk. According to our meta-analysis results, relative to acitretin monotherapy, XYP plus acitretin increased the total clinical effective rate, as evidenced by Psoriasis area and severity index score (PASI)-20, PASI-30 and PASI-60 in patients with PV [risk ratio (RR) = 1.23 Z = 4.87, p < 0.00001, 95% confidence interval (CI): 1.13–1.34; RR = 1.29, Z = 3.89, p = 0.009, 95% CI: 1.07 to 1.55; and RR = 1.31, Z = 3.89, p = 0.0001, 95% CI: 1.14–1.49]; the reduced levels of TNF-α, MCP-1 and RANTES, the alleviated side effects resulting from acitretin like itchiness (RR = 0.54, 95% CI: 0.4 to 0.74, Z = 3.94, p < 0.0001), and the increased levels of aminotransferases and dyslipidemia (RR = 0.5, 95%CI = 0.29, 0.86, p = 0.01; and RR = 0.41, 95% CI = 0.23, 0.75, p = 0.004). Conclusion: As suggested in the present meta-analysis, XYP combined with acitretin effectively and safely treats PV. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022333273 , identifier PROSPERO 2022 CRD42022333273.

Background This study explores the relationship between smartphone addiction and sleep quality, and to further assess the mediating role of loneliness and depression. Methods A survey of 200 older adults individuals was conducted using the Smartphone Addiction Scale-Short Version (SAS-SV) for smartphone addiction, Pittsburgh Sleep Quality Index (PSQI) for sleep quality, Geriatric Depression Scale-15 (GDS-15) for depression, and DeJong Gierveld Loneliness Scale (DGLS) for loneliness. Linear regression and mediation analysis were performed for statistical analysis. Results A negative causal relationship was observed between smartphone addiction and sleep quality in the older adults ( p  < 0.05). Depression and loneliness in the older adults may potentially exacerbate the effect of smartphone addiction on sleep quality ( p  < 0.05). Conclusion Individuals with smartphone addiction appeared to have poorer sleep quality, psychological factors play a mediating role in the association between smartphone addiction and sleep quality in the older adults. This emphasizes the importance of care for the mental health of the older adults and recognizes the negative impact of smartphone addiction on their quality of life.

To investigate differentially expressed genes regulated by microRNA-451a in colorectal cancer. We detected expression of microRNA-451a in colorectal cancer samples and normal pericarcinous tissues from 68 colorectal cancer patients and the correlation between microRNA-451a and clinical features of these patients. Then, the expression of microRNA-451a in HCT116, SW620, HT29, SW480, and DLD cells was also measured. The suppression subtractive hybridization method was used with two HCT116 cell lines with overexpressing or underexpressing microRNA-451a, respectively. The most highly increased genes were screened. Their functions were predicted by gene ontology analysis. The expression ratio of microRNA-451a in colorectal cancer to pericarcinous tissues was 0.37. Expression of microRNA-451a was decreased in HCT116, SW620, HT29, SW480, and DLD cells. In our suppression subtractive hybridization library, expression of seven genes was the most highly increased when underexpressing microRNA-451a. They were BCAP31, EEF1A1, CDC20, WDR6, TUFM, RPL13, and RPL7A. Expression of DKK1, PSME1, NDUFA3, and GNB2 was most highly increased when overexpressing microRNA-451a. Gene ontology analysis showed that the main functions of these genes were associated with translational elongation, protein localization to the endoplasmic reticulum, translation, poly(A) RNA binding, negative regulations of Wnt signaling pathway, and so on. MicroRNA-451a was demonstrated to be downregulated in colorectal cancer patient tissues whose target genes were analyzed and functions were predicted by suppression subtractive hybridization.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers, yet the molecular mechanisms underlying its onset and development have not yet been fully elucidated. Indeed, an in-depth understanding of the potential molecular mechanisms underlying HNSCC oncogenesis may aid the development of better treatment strategies. Recent epigenetic studies have revealed that the m6A RNA modification plays important roles in HNSCC. In this review, we summarize the role of m6A modification in various types of HNSCC, including thyroid, nasopharyngeal, hypopharyngeal squamous cell, and oral carcinoma. In addition, we discuss the regulatory roles of m6A in immune cells within the tumor microenvironment, as well as the potential molecular mechanisms. Finally, we review the development of potential targets for treating cancer based on the regulatory functions of m6A, with an aim to improving targeted therapies for HNSCC. Together, this review highlights the important roles that m6A modification plays in RNA synthesis, transport, and translation, and demonstrates that the regulation of m6A-related proteins can indirectly affect mRNA and ncRNA function, thus providing a novel strategy for reengineering intrinsic cell activity and developing simpler interventions to treat HNSCC.

ObjectiveBoth sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes.MethodsTotally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes.ResultsGQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267–5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482–6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218–13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT.ConclusionSeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

The aim of this study was to observe the rotation patterns at the papillary muscle plane in the Left Ventricle(LV) with normal subjects using two-dimensional speckle tracking imaging(2D-STI). We acquired standard of the basal, the papillary muscle and the apical short-axis images of the LV in 64 subjects to estimate the LV rotation motion by 2D-STI. The rotational degrees at the papillary muscle short-axis plane were measured at 15 different time points in the analysis of two heart cycles. There were counterclockwise rotation, clockwise rotation, and counterclockwise to clockwise rotation at the papillary muscle plane in the LV with normal subjects, respectively. The ROC analysis of the rotational degrees was performed at the papillary muscle short-axis plane at the peak LV torsion for predicting whether the turnaround point of twist to untwist motion pattern was located at the papillary muscle level. Sensitivity and specificity were 97% and 67%, respectively, with a cut-off value of 0.34°, and an area under the ROC curve of 0.8. At the peak LV torsion, there was no correlation between the rotational degrees at the papillary muscle short-axis plane and the LVEF in the normal subjects(r = 0.000, p = 0.998). In the study, we conclude that there were three rotation patterns at the papillary muscle short-axis levels, and the transition from basal clockwise rotation to apical counterclockwise rotation is located at the papillary muscle level.