ANP32B promotes colorectal cancer cell progression and reduces cell sensitivity to PRAP1 inhibitor through up-regulating HPF1.

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

The treatment of patients with non-small cell lung cancer carrying uncommon EGFR mutations, HER2 mutations, or brain metastases: a systematic review of pre-clinical and clinical findings for dacomitinib.

Background: Accumulating evidence has shown that dacomitinib has potential activities for patients with non-small cell lung cancer (NSCLC) harboring uncommon epidermal growth factor receptor (EGFR) mutations, human epidermal growth factor receptor 2 (HER2) mutations, or central nervous system (CNS) metastases. Methods: This study aimed to give a systematic review on its potential applications in the above settings by searching MEDLINE/PubMed, Embase, Cochrane Library, American Society of Clinical Oncology.org, European Society for Medical Oncology.org, and ClinicalTrials.gov. Results: The literature search yielded 649 publications in total. According to our findings, dacomitinib exhibited promising efficacy in patients with major uncommon EGFR mutations (including G719X, S768I, and L861Q). Both EGFR exon 20 insertional mutation (Ex20ins) and HER2 Ex20ins demonstrated significant internal heterogeneity in response to dacomitinib, among which specific subtypes (including EGFR D770delinsGY, A763_Y764insFQEA, and HER2 M774delinsWLV) were highly sensitive. Other uncommon EGFR mutations including 18del and L747P have also been shown responsive to dacomitinib. Interestingly, limited studies suggested dacomitinib application on certain first or third generation tyrosine kinase inhibitors (TKIs)' resistant secondary mutations. Last but not least, both pre-clinical and clinical data indicated that dacomitinib has an encouraging intracranial tumor control ability, regardless of uncommon mutations. Conclusions: Dacomitinib demonstrated good disease control on patients with NSCLC harboring major uncommon EGFR mutations and specific EGFR or HER2 mutation subtypes, and selective clinical application of dacomitinib is considerable in this setting, especially for those with intracranial metastases.

IL-7 promotes CD19-directed CAR-T cells proliferation through miRNA-98-5p by targeting CDKN1A.

CAR-T targeting CD19 have achieved significant effects in the treatment of B-line leukemia and lymphoma. However, the treated patients frequently relapsed and could not achieve complete remission. Therefore, improving the proliferation and cytotoxicity of CAR-T cells, reducing exhaustion and enhancing infiltration capacity are still issues to be solved. The IL-7 has been shown to enhance the memory characteristics of CAR-T cells, but the specific mechanism has yet to be elaborated. miRNAs play an important role in T cell activity. However, whether miRNA is involved in the activation of CAR-T cells by IL-7 has not yet been reported. Our previous study had established the 3rd generation CAR-T cells. The present study further found that IL-7 significantly increased the proliferation of anti-CD19 CAR-T cells, the ratio of CD4 + CAR + cells and the S phase of cell cycle. In vivo study NAMALWA xenograft model showed that IL-7-stimulated CAR-T cells possessed stronger tumoricidal efficiency. Further we validated that IL-7 induced CAR-T cells had low expression of CDKN1A and high expression of miRNA-98-5p. Additionally, CDKN1A was associated with miRNA-98-5p. Our results, for the first time, suggested IL-7 could conspicuously enhance the proliferation of CAR-T cells through miRNA-98-5p targeting CDKN1A expression, which should be applied to CAR-T production.

Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Serotonin/5-HT7 receptor provides an adaptive signal to enhance pigmentation response to environmental stressors through cAMP-PKA-MAPK, Rab27a/RhoA, and PI3K/AKT signaling pathways.

Serotonin (5-HT), a neurotransmitter, is essential for normal and pathological pigmentation processing, and its receptors may be therapeutical targets. The effect and behavior of the 5-HT7 receptor (5-HT7R) in melanogenesis in high vertebrates remain unknown. Herein, we examine the role and molecular mechanism of 5-HT7R in the pigmentation of human skin cells, human tissue, mice, and zebrafish models. Firstly, 5-HT7R protein expression decreased significantly in stress-induced depigmentation skin and vitiligo epidermis. Stressed mice received transdermal serotonin 5-HT7R selective agonists (LP-12, 0.01%) for 12 or 60 days. Mice might recover from persistent stress-induced depigmentation. The downregulation of tyrosinase (Tyr), microphthalmia-associated transcription factor (Mitf) expression, and 5-HT7R was consistently restored in stressed skin. High-throughput RNA sequencing showed that structural organization (dendrite growth and migration) and associated pathways were activated in the dorsal skin of LP-12-treated animals. 5-HT7R selective agonist, LP-12, had been demonstrated to enhance melanin production, dendrite growth, and chemotactic motility in B16F10 cells, normal human melanocytes (NHMCs), and zebrafish. Mechanistically, the melanogenic, dendritic, and migratory functions of 5-HT7R were dependent on the downstream signaling of cAMP-PKA-ERK1/2, JNK MAPK, RhoA/Rab27a, and PI3K/AKT pathway activation. Importantly, pharmacological inhibition and genetic siRNA of 5-HT7R by antagonist SB269970 partially/completely abolished these functional properties and the related activated pathways in both NHMCs and B16F10 cells. Consistently, htr7a/7b genetic knockdown in zebrafish could blockade melanogenic effects and abrogate 5-HT-induced melanin accumulation. Collectively, we have first identified that 5-HT7R regulates melanogenesis, which may be a targeted therapy for pigmentation disorders, especially those worsened by stress.

Construction and validation of postoperative hypothermia prediction model for patients undergoing joint replacement surgery.

AIM: To construct and validate a postoperative hypothermia prediction model for patients undergoing joint replacement surgery. BACKGROUND: Postoperative hypothermia is one of the harmful perioperative complications in patients undergoing joint replacement surgery. The previous studies mainly focused on intraoperative hypothermia prediction models. The prediction model for postoperative hypothermia in patients with joint replacement surgery was understudied. DESIGN: Cohort study. METHODS: We collected data from 503 participants undergoing joint replacement surgery in a tertiary hospital from January 2019 to December 2021. Of those, 404 cases were assigned to the modelling and 99 to the validation groups. Logistic regression was used to construct the model. The AUC was used to test the predictive effect of the model. Finally, 99 cases were used to verify the application effect of the model. A TRIPOD checklist was used to guide the reporting of this study. RESULTS: The factors entered into the prediction model were age, intraoperative hypothermia, BMI, heat preservation measures and platelet (PLT). The model was constructed as follows: Logit (P) = .537 + 3.669 × 1 (intraoperative hypothermia) + .030 × age - .289 × BMI + 2.857 × 1 (intraoperative insulation measures) + .003 × PLT. Hosmer-Lemeshow test, p = .608, the area under the receiver operating characteristic curve (AUC) was .861. The Youden index was .530, the sensitivity was .599 and the specificity was .93. The incidence of postoperative hypothermia in the modelling group was 42.93% (173/404), and that in the verification group was 43.43% (43/99), χ2 = .012, p = .912. The correct practical application rate was 87.88%. This model has a good application effect. CONCLUSION: The current prediction model provided a reference for clinical screening of patients with high-risk hypothermia after joint replacement surgery. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses can use the developed prediction model to predict the occurrence of postoperative hypothermia and provide a reference for the preventive measure.

Acute pulmonary embolism originating from upper limb venous thrombosis following breast cancer surgery: Two case reports.

BACKGROUND: Upper limb venous thrombosis (ULVT) is rarer than lower-extremity deep venous thrombosis, and is related to Paget-Schroetter syndrome, central venous catheterization, and malignancy. There are few reports of pulmonary embolism (PE) from upper-extremity vein thrombosis due to surgery. Herein, we report two cases of PE that originated from upper limb venous thrombosis on the surgical side in two patients undergoing modified radical mastectomy for breast cancer. These cases challenge the traditional theory that PE originate only from the lower extremities. CASE SUMMARY: We describe two female patients, aged 68 and 65 years, respectively, who had undergone modified radical mastectomy for breast cancer. They did not have a central venous catheter and did not undergo preoperative neoadjuvant chemotherapy. They were transferred to the intensive care unit due to symptomatic PE on the first day after surgery. Colour Doppler ultrasound identified fresh thrombosis in their upper limb veins, which was the presumed source of the PE. They all received anticoagulation therapy, and one of them experienced bleeding that required discontinuation of the drug. Ultimately, they were discharged in stable condition. CONCLUSION: ULVT as a source of PE after breast cancer surgery cannot be ignored.

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/ß-catenin pathway.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover， western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.

Functional implications of PABPC1 in the development of ovarian cancer.

This research aimed to probe the expression characteristics of poly(A)-binding protein cytoplasmic 1 (PABPC1) and its role on the phenotype of ovarian cancer (OC) cells and to further investigate the possible underlying mechanism. The expression of PABPC1 was analyzed according to the data from gene expression omnibus, The Cancer Genome Atlas (TCGA) and Oncomine databases and the RNA sequencing data set from TCGA were downloaded for evaluating the prognostic values. We revealed that compared with the healthy samples, PABPC1 was upregulated in OC samples. High expression of PABPC1 had a connection with a shorter survival for patients with OC. Loss and gain of function assays revealed that silencing PABPC1 significantly suppressed the viability, invasion and migration of SK-OV-3 cells, while PABPC1 overexpression in A2780 cells showed the reverse outcomes. Moreover, Western blot demonstrated that silencing PABPC1 notably inactivated the epithelial-mesenchymal transition (EMT) process, while upregulation of PABPC1 promoted the mitigation of epithelial phenotype and the acquisition of mesenchymal phenotype. Taken together, PABPC1 was upregulated in OC cells and served as a carcinogene to promote the OC cell growth and invasion partly by modulating the EMT process, which implied that PABPC1 might be considered as a useful biomarker for OC therapeutics.

[Clinical observation of transforaminal endoscopy combined with interspinous fusion in the treatment of lumbar spinal stenosis with instability in the elderly].

OBJECTIVE: To observe the clinical effect of transforaminal endoscopy combined with interspinous fusion in the treatment of lumbar spinal stenosis with instability in the elderly. METHODS: From February 2018 to February 2019, 82 elderly patients with lumbar spinal stenosis and instability were divided into control group and observation group. In the control group, there were 23 males and 18 females;the age was (68.9±4.1) years;the course of disease was (14.1±5.7) months;there were 5 cases of single segment lesions and 36 cases of multi segment lesions;simple bacfuse interspinous fusion was used. In the observation group, there were 22 males and 19 females;the age was (69.1±4.0) years;the course of diseasewas (14.4±5.5) months;there were 6 cases of single segment lesions and 35 cases of multi segment lesions;they were treated with transforaminal endoscopic surgery combined with Bacfuse interspinous fusion. The clinical efficacy, visual analogue scale (VAS), Japanese Orthopaedic Association scores (JOA), Oswestry disability index (ODI), Lehmann lumbar function score, posterior disc height and intervertebral foramen height, complication rate and recurrence rate of the two groups were compared. RESULTS: The clinical efficacy of the observation group was better than that of the control group;the VAS score of the observation group was lower than that of the control group, the JOA score was higher than that of the control group, and the ODI index at 3 months after operation and at the last follow-up was lower than that of the control group, the Lehmann lumbar function score was higher than that of the control group;the posterior edge height of intervertebral disc and intervertebral foramen height were higher than those of the controlgroup;the incidence of complications and recurrence rate (4.9% and 0.0%) of the observation group were lower than those of the control group (19.5%, 9.8%), the difference was statistically significant (P<0.05). CONCLUSION: The clinical effect of transforaminal endoscopy combined with interspinous process fusion in the treatment of lumbar spinal stenosis with instability in the elderly is ideal. It can reduce postoperative pain, improve lumbar function, improve the height of posterior edge of intervertebral disc and intervertebral foramen, and reduce the incidence and recurrence rate. It is worthy of clinical promotion.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Ameliorate HaCaT Cell Photo-Aging.

Umbilical cord mesenchymal stem cells (UCMSCs) have been identified as a potentially ideal cell type for use in regenerative therapeutic contexts owing to their excellent paracrine secretory abilities and other desirable properties. Previous work has shown that stem cell-derived exosomes can effectively reduce skin aging, but few studies have specifically focused on the role of UCMSC-derived exosomes in this context. In this study, we isolated exosomes derived from UCMSCs grown in a three-dimensional culture system and explored their ability to modulate the photo-aging of HaCaT keratinocytes. Cell viability and proliferation were assessed using CCK8 assay, whereas wound healing and transwell assays were used to assess cell migratory capabilities. UVB irradiation (60 mJ/cm2) was used to induce photo-aging of HaCaT cells. TUNEL and SA-ß-Gal staining were used to explore HaCaT cell apoptosis and senescence, respectively, whereas real-time quantitative PCR was used to assess the expression of relevant genes at the mRNA level. We found that UCMSC-derived exosomes were able to enhance normal HaCaT cell proliferation and migration while also inhibiting UVB-induced damage to these cells. These exosomes also reduced HaCaT cell apoptosis and senescence, increasing collagen type I expression and reducing matrix metalloproteinase (MMP1) expression in photo-aged HaCaT cells. Together, these findings indicate that UCMSC-derived exosomes have the potential to be used therapeutically to suppress skin aging.

Evaluation of piggyBac-mediated anti-CD19 CAR-T cells after ex vivo expansion with aAPCs or magnetic beads.

Adoptive immunotherapy is a new potential method of tumour therapy, among which anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T cell), is a typical treatment agent for haematological malignancies. Previous clinical trials showed that the quality and phenotype of CAR-T cells expanded ex vivo would seriously affect the tumour treatment efficacy. Although magnetic beads are currently widely used to expand CAR-T cells, the optimal expansion steps and methods have not been completely established. In this study, the differences between CAR-T cells expanded with anti-CD3/CD28 mAb-coated beads and those expanded with cell-based aAPCs expressing CD19/CD64/CD86/CD137L/mIL-15 counter-receptors were compared. The results showed that the number of CD19-specific CAR-T cells with a 4-1BB and CD28 co-stimulatory domain was much greater with stimulation by aAPCs than that with beads. In addition, the expression of memory marker CD45RO was higher, whereas expression of exhausted molecules was lower in CAR-T cells expanded with aAPCs comparing with the beads. Both CAR-T cells showed significant targeted tumoricidal effects. The CAR-T cells stimulated with aAPCs secreted apoptosis-related cytokines. Moreover, they also possessed marked anti-tumour effect on NAMALWA xenograft mouse model. The present findings provided evidence on the safety and advantage of two expansion methods for CAR-T cells genetically modified by piggyBac transposon system.

Remarkable Response of EGFR- and HER2-Amplified Metastatic Colon Cancer to Pyrotinib After Failed Multiline Treatments: A Case Report and Literature Review.

Human epidermal growth factor receptor 2 (HER2) has been verified as a valuable biomarker and treatment target in metastatic colorectal cancer (mCRC). Pyrotinib, a novel irreversible HER2/epidermal growth factor receptor (EGFR) dual tyrosine kinase inhibitor, can efficiently inhibit the proliferation of HER2-positive cancer cells in many tumors. We report a case of a 40-year-old woman with both HER2- and EGFR-amplified metastatic colon cancer, who developed refractory disease resistant to multiline therapies (including trastuzumab with lapatinib) but achieved a remarkable response after pyrotinib treatment. For patients with HER2-positive mCRC, who have developed resistance to trastuzumab and lapatinib, pyrotinib is a promising new candidate, which can be used as salvage therapy.

Adenosquamous carcinoma of the digestive system: a literature review.

Adenosquamous carcinoma (ASC), containing both adenocarcinoma and squamous cell carcinoma components, is rare in the digestive system. Limited data is available on ASC of the digestive system (AS-ASC), and the current evidence is available mainly in the form of case reports and case series. We performed a thorough search of the available literature and compiled a review on the epidemiology, histopathology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of AS-ASC. Non-specific clinical and imaging presentations and low diagnostic accuracy of biopsy lead to difficulties in preoperative diagnosis in a high proportion of patients and high malignancy. The pathogenesis remains obscure. Surgery remains the mainstay of treatment for AS-ASC. The role of chemoradiotherapy as an adjuvant treatment is still inconclusive. Key messages Metastatic linings and the lack of efficacious treatments lead to an unfavorable outcome in AS-ASC patients. Further research could help us understand the pathophysiology of AS-ASCand the unique needs of AS-ASC patients.

Computational methods for recognition of cancer protein markers in saliva.

In recent years, many studies have supported that cancer tissues can make disease-specific changes in some salivary proteins through some mediators in the pathogenesis of systemic diseases. These salivary proteins have the potential to become cancer-specific biomarkers in the early diagnosis stage. How to effectively identify these potential markers is one of the challenging issues. In this paper, we propose novel machine learning methods for recognition cancer biomarkers in saliva by two stages. In the first stage, salivary secreted proteins are recognized which are considered as candidate biomarkers of cancers. We picked up 557 salivary secretory proteins from 20379 human proteins by public databases and published literatures. Then, we present a training set construction strategy to solve the imbalance problem in order to make the classification methods get better accuracy. From all human protein set, the proteins belonging to the same families as salivary secretory proteins are removed. After that, we use SVC-KM method to cluster the remaining proteins, and select negative samples from each cluster in proportion. Next, the features of proteins are calculated by tools. We collect 24 protein properties such as sequence, structure and physicochemical properties, a total of 1087 features. An innovative procedure based on the local samples is proposed for selecting the appropriate features, in order to further improve the performance of SVM classifier. Experimental results show that the average sensitivity, specificity and accuracy of salivary secretory protein recognition using selected 32 features in training set are 97.09%, 98.10%, 97.61%, respectively. The use of these methods can improve the accuracy of recognition by solving the problems of unbalanced sample size and uneven distribution in training set. In the second stage, we apply the best model to dig out the salivary secreted proteins from 58 reported cancer markers, and get a total of 42 proteins which are considered to be used for salivary diagnosis. We analyze the gene expression data of three types of cancer, and predict that 33 genes will appear in saliva after they are translated into proteins. This study provides an important computational tool to help biologists and researchers reduce the number of candidate proteins and the cost of research. So as to further accelerate the discovery of cancer biomarkers in saliva and promote the development of saliva diagnosis.

MCTR1 alleviates lipopolysaccharide-induced acute lung injury by protecting lung endothelial glycocalyx.

Endothelial glycocalyx degradation, critical for increased pulmonary vascular permeability, is thought to facilitate the development of sepsis into the multiple organ failure. Maresin conjugates in tissue regeneration 1 (MCTR1), a macrophage-derived lipid mediator, which exhibits potentially beneficial effects via the regulation of bacterial phagocytosis, promotion of inflammation resolution, and regeneration of tissue. In this study, we show that MCTR1 (100 ng/mouse) enhances the survival of mice with lipopolysaccharide (LPS)-induced (15 mg/kg) sepsis. MCTR1 alleviates LPS (10 mg/kg)-induced lung dysfunction and lung tissue inflammatory response by decreasing inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß [IL-1ß], and IL-6) expression in serum and reducing the serum levels of heparan sulfate (HS) and syndecan-1. In human umbilical vein endothelial cells (HUVECs) experiments, MCTR1 (100 nM) was added to the culture medium with LPS for 6 hr. MCTR1 treatment markedly inhibited HS degradation by downregulating heparanase (HPA) protein expression in vivo and in vitro. Further analyses indicated that MCTR1 upregulates sirtuin 1 (SIRT1) expression and decreases NF-κB p65 phosphorylation. In the presence of BOC-2 or EX527, the above effects of MCTR1 were abolished. These results suggest that MCTR1 protects against LPS-induced sepsis in mice by attenuating pulmonary endothelial glycocalyx injury via the ALX/SIRT1/NF-κB/HPA pathway.

Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis.

BACKGROUND: Postoperative peritoneal adhesion (PPA), characterized by abdominal pain, female infertility, and even bowel obstruction after surgery, has always been a major concern. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms underlying the basis of microarray data profile, followed by peritoneal adhesion formation, are largely unknown. AIM: To reveal the underlying pathogenesis of PPA at the molecular level. METHODS: The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis. We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods. We performed quantitative PCR and western blotting in vivo to validate the results preliminarily. RESULTS: In total, 446 expressed genes were altered in peritoneal adhesion. We found that several hub genes (e.g., tumor necrosis factor, interleukin 1 beta, interleukin 6, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2) were marked as significant biomarkers. Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway. According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies, TLR4, myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa B (NF-κB) played essential roles in Toll-like signaling transduction. Here, we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion. The results of the microarray analysis were verified by the animal experiments. These findings may extend our understanding of the molecular mechanisms of PPA. CONCLUSION: The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA. Future studies are required to validate our findings.

HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway.

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-γ, IL-4, HXTF-medicated serum, and PPAR-γ agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR-γ nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-γ) nuclear translocation. Furthermore, the use of HXTF and PPAR-γ agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR-γ agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR-γ pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR-γ pathway.