Role of artificial intelligence in digital pathology for gynecological cancers.

The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored.

Laparoscopic vs open surgery for gastric cancer: Assessing time, recovery, complications, and markers.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. Morbidity and mortality have increased in recent years, making it an urgent issue to address. Laparoscopic radical surgery (LRS) is a crucial method for treating patients with GC; However, its influence on tumor markers is still under investigation. AIM: To determine the effects of LRS on patients with GC and their serum tumor markers. METHODS: The data of 194 patients treated at Chongqing University Cancer Hospital between January 2018 and January 2019 were retrospectively analyzed. Patients who underwent traditional open surgery and LRS were assigned to the control (n = 90) and observation groups (n = 104), respectively. Independent sample t-tests and χ2 tests were used to compare the two groups based on clinical efficacy, changes in tumor marker levels after treatment, clinical data, and the incidence of postoperative complications. To investigate the association between tumor marker levels and clinical efficacy in patients with GC, three-year recurrence rates in the two groups were compared. RESULTS: Patients in the observation group had a shorter duration of operation, less intraoperative blood loss, an earlier postoperative eating time, and a shorter hospital stay than those in the control group (P < 0.05). No significant difference was observed between the two groups regarding the number of lymph node dissections (P > 0.05). After treatment, the overall response rate in the control group was significantly lower than that in the observation group (P = 0.001). Furthermore, after treatment, the levels of carbohydrate antigen 19-9, cancer antigen 72-4, carcinoembryonic antigen, and cancer antigen 125 decreased significantly. The observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group (P < 0.001). Additionally, the two groups did not significantly differ in terms of three-year survival and recurrence rates (P > 0.05). CONCLUSION: LRS effectively treats early gastric cancer by reducing intraoperative bleeding, length of hospital stays, and postoperative complications. It also significantly lowers tumor marker levels, thus improving the short-term prognosis of the disease.

TC2N inhibits distant metastasis and stemness of breast cancer via blocking fatty acid synthesis.

BACKGROUND: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood. METHODS: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays. RESULTS: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level. CONCLUSIONS: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer.

Chemical Composition and Antibacterial and Antiulcerative Colitis Activities of Essential Oil from Pruni Semen.

This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.

Proteomic characterization of epithelial ovarian cancer delineates molecular signatures and therapeutic targets in distinct histological subtypes.

Clear cell carcinoma (CCC), endometrioid carcinoma (EC), and serous carcinoma (SC) are the major histological subtypes of epithelial ovarian cancer (EOC), whose differences in carcinogenesis are still unclear. Here, we undertake comprehensive proteomic profiling of 80 CCC, 79 EC, 80 SC, and 30 control samples. Our analysis reveals the prognostic or diagnostic value of dysregulated proteins and phosphorylation sites in important pathways. Moreover, protein co-expression network not only provides comprehensive view of biological features of each histological subtype, but also indicates potential prognostic biomarkers and progression landmarks. Notably, EOC have strong inter-tumor heterogeneity, with significantly different clinical characteristics, proteomic patterns and signaling pathway disorders in CCC, EC, and SC. Finally, we infer MPP7 protein as potential therapeutic target for SC, whose biological functions are confirmed in SC cells. Our proteomic cohort provides valuable resources for understanding molecular mechanisms and developing treatment strategies of distinct histological subtypes.

[Xixin Decoction improves learning and memory ability of SAMP8 by enhancing neuroprotective effect and inhibiting neuroinflammation].

This study aimed to explore the possible effect of Xixin Decoction(XXD) on the learning and memory ability of Alzheimer's disease(AD) model senescence-accelerated mouse-prone 8(SAMP8) and the related mechanism in enhancing neuroprotective effect and reducing neuroinflammation. Forty SAMP8 were randomly divided into a model group(10 mL·kg~(-1)·d~(-1)), a probiotics group(0.39 g·kg~(-1)·d~(-1)), a high-dose group of XXD granules(H-XXD, 5.07 g·kg~(-1)·d~(-1)), a medium-dose group of XXD granules(M-XXD, 2.535 g·kg~(-1)·d~(-1)), and a low-dose group of XXD granules(L-XXD, 1.267 5 g·kg~(-1)·d~(-1)). Eight senescence-accelerated mouse-resistant 1(SAMR1) of the same age and strain were assigned to the control group(10 mL·kg~(-1)·d~(-1)). After ten weeks of intragastric administration, the Morris water maze was used to test the changes in spatial learning and memory ability of mice after treatment. Meanwhile, immunofluorescence staining was used to detect the positive expression of receptor for advanced glycation end products(AGER), Toll-like receptor 1(TLR1), and Toll-like receptor 2(TLR2) in the hippocampal CA1 region of mice. Western blot was employed to test the protein expression levels of silencing information regulator 2 related enzyme 1(SIRT1), AGER, TLR1, and TLR2 in the hippocampus of mice. Enzyme linked immunosorbent assay(ELISA) was applied to assess the levels of Aß_(1-42) in the hippocampus of mice and the levels of nuclear factor κB p65(NF-κB p65), NOD-like receptor protein 3(NLRP3), tumor necrosis factor-α(TNF-α), and interleukin-1ß(IL-1ß) in the serum and hippocampus of mice. Compared with the model group, XXD significantly improved the spatial learning and memory ability of SAMP8, increased the expression of neuroprotective factors in the hippocampus, decreased the levels of neuroinflammatory factors, and inhibited the expression of Aß_(1-42). In particular, H-XXD significantly increased the expression of SIRT1 in the hippocampus of mice, reduced the expression levels of NF-κB p65, NLRP3, TNF-α, and IL-1ß in the serum and hippocampus of mice, and decreased the expression of AGER, TLR1, and TLR2 in the hippocampus of mice(P<0.05 or P<0.01). XXD may improve the spatial learning and memory ability of AD model SAMP8 by enhancing the neuroprotective effect and inhibiting neuroinflammation.

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.

Rat tight junction proteins are disrupted after subchronic exposure to okadaic acid.

Okadaic acid (OA), a lipophilic phycotoxin distributed worldwide, causes diarrheic shellfish poisoning and even leads to tumor formation. Currently, the consumption of contaminated seafood is the most likely cause of chronic OA exposure, but there is a serious lack of relevant data. Here, the Sprague-Dawley rats were exposure to OA by oral administration at 100 µg/kg body weight, and the tissues were collected and analyzed to assess the effect of subchronic OA exposure. The results showed that subchronic OA administration disturbed colonic mucosal integrity and induced colitis. The colonic tight junction proteins were disrupted and the cell cycle of colonic epithelial cells was accelerated. It is inferred that disruption of the colonic tight junction proteins might be related to the development of chronic diarrhea by affecting water and ion transport. Moreover, the accelerated proliferation of colonic epithelial cells indicated that subchronic OA exposure might promote the restitution process of gut barrier or induce tumor promoter activity in rat colon.

p-Synephrine ameliorates alloxan-induced diabetes mellitus through inhibiting oxidative stress and inflammation via suppressing the NF-kappa B and MAPK pathways.

Oxidative stress and inflammation play important roles in the development of diabetes mellitus. p-Synephrine, the primary pharmacologically active protoalkaloid in Citrus species, has been popularly consumed as a dietary supplement for weight loss management. However, the effects of p-synephrine on diabetes mellitus and the action mechanisms have not been clearly elucidated. In this study, the in vitro antioxidant effects of p-synephrine were evaluated. The data showed that p-synephrine treatment exhibited significant scavenging effects against DPPH, ABTS and OH radicals and showed high reducing power. Diabetic mice were developed by alloxan injection, followed by p-synephrine administration to investigate its hypoglycemic effects in vivo. The results showed that p-synephrine intervention significantly prevented alloxan-induced alteration in body weight, organ indexes, serum uric acid content and serum creatinine content. Meanwhile, p-synephrine application significantly improved the lipid profiles, superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) contents in the serum and kidneys of diabetic mice and reduced the malondialdehyde (MDA) content in the serum of diabetic mice. Further assays suggested that p-synephrine treatment improved alloxan-induced decreases of glucose tolerance and insulin sensitivity. Also, p-synephrine supplementation altered histopathological changes in the kidneys and interscapular brown adipose tissues in diabetic mice. In addition, p-synephrine administration inhibited renal inflammation through suppressing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) gene expression levels, as well as CD45 expression levels. The anti-inflammatory effects were probably involved in the regulation of nuclear factor-κB (NF-κB) activation and mitogen-activated protein kinase (MAPK) phosphorylation. In conclusion, p-synephrine application significantly ameliorated alloxan-induced diabetes mellitus by inhibiting oxidative stress via suppressing the NF-κB and MAPK pathways.

Serum BLMH and CKM as Potential Biomarkers for Predicting Therapeutic Effects of Deep Brain Stimulation in Parkinson's Disease: A Proteomics Study.

BACKGROUND: Deep brain stimulation (DBS) is recommended for the treatment of advanced Parkinson's disease (PD), though individual reactions may be different. There are currently no clinically available biomarkers for predicting the responses of PD patients to DBS before surgery. This study aimed to determine serum biomarkers to predict DBS responses in PD. METHODS: We profiled differentially expressed proteins (DEPs) in serum samples and identified potential biomarkers to predict the therapeutic responses to DBS in PD patients. Ten serum samples were selected from PD patients to identify DEPs via mass spectrometry proteomics; these were then verified by enzyme-linked immunosorbent assay in another 21 serum samples of PD patients. RESULTS: The present study identified 14 DEPs (10 downregulated and four upregulated DEPs) with significantly different levels between non-responders and responders. Most of the DEPs were related to amino acid metabolism and protein modification pathways. Bleomycin hydrolase (BLMH) and creatine kinase M-type (CKM) were found to be significantly downregulated in the responders. Additionally, subsequent logistic regression and receiver operating characteristic analyses were performed to determine the diagnostic performance of candidate proteins. CONCLUSIONS: The identified DEPs show potential as biomarkers for the accurate evaluation of DBS therapeutic responses before surgery. Furthermore, assessment of serum BLMH and CKM may be particularly useful for predicting the therapeutic responses to DBS in PD patients.

Synthesis and anti-ovarian cancer effects of benzimidazole-2-substituted pyridine and phenyl propenone derivatives.

Background: Given the benzimidazole derivatives have anti-ovarian cancer effects, the authors aimed to determine whether benzimidazole-2-substituted pyridine and phenyl propenone derivatives exert anti-ovarian cancer activity. Materials & methods: 21 derivatives were synthesized and assayed for their antiproliferative activities. Western blotting in A2780 cells was used to detect the effects of compound A-6 on apoptosis-related proteins. Invasion, migration and apoptosis were assayed in SKOV3 cells treated with A-6. The in vivo activity was also examined. Results: A-6 could inhibit proliferation, invasion and migration and induce apoptosis in SKOV3 cells. Additionally, A-6 had potent inhibitory activity in a xenograft mouse model. Conclusion: A-6 shows potent efficacy in the treatment of ovarian cancer and may be a potential antitumor agent.

Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination: A retrospective analysis.

BACKGROUND: Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD) is a serious complication of GBM that often results in dire outcomes. There is currently no effective treatment. AIM: To estimate the clinical outcomes of combination therapy in GBM patients with LMD. METHODS: A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution. All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate (MTX) and systemic chemotherapy. Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment. RESULTS: Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 mo (range: 2-59 mo). The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo (range: 2-59 mo). In the Cox univariate analysis, gross resection of tumor (P = 0.022), Karnofsky performance status (KPS) > 60 (P = 0.002), and Ommaya reservoir implant (P < 0.001) were correlated with survival. Multivariate analysis showed that KPS > 60 (P = 0.037) and Ommaya reservoir implant (P = 0.014) were positive factors correlated with survival. Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy. According to Common Terminology Criteria of Adverse Events 4.03, most of the patients presented with toxicity less than grade 3. CONCLUSION: Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD, with mild treatment-related side effects.

Characterization and function of biomarkers in sunitinib-resistant renal carcinoma cells.

OBJECTIVE: Sunitinib is a first-line drug in the treatment of metastatic renal cell carcinoma, but patients will inevitably develop drug resistance after 6-15 months of systematic treatment, which seriously affects the prognosis in KIRC. METHODS: During the study, the Gene Expression Omnibus (GEO) database was used to perform a systematic bioinformatics analysis,so that we could determine the genes (DEGs) which are differentially expressed between sunitinib-sensitive and sunitinib-resistant RCC (SRRC) cells. RESULTS: A total of 31 DEGs were identified. Gene ontology (GO) was used to analyze the function of DEGS. These DEGs were found mainly enriched in organic aniontransmembrane transporter. The Cytohubba plug-in, STRING database and Cytoscape software were involved to construct a protein-protein interaction (PPI) network, and the pivot genes were identified by single-gene and multi-gene Cox regression analysis. Finally, DDX58 and MX2 were identified as prognostic genes. Survival analysis was performed by using prognostic nomogram, prognostic histogram and GEPIA database to verify the relationship between DDX58 and MX2 expression and survival. The relationship between the two pivot genes and the prognosis of patients was further verified by using the KM survival analyses and Time Dependency ROC curve analyses from TCGA database. Immunohistochemical analyses confirmed that, in tumor tissues and normal tissues, DDX58 and MX2 were differentially expressed. The expression of these two genes have relationship with the immune checkpoint. CONCLUSIONS: This study provides insights into the molecular mechanisms of SRRC, as well as the selection of therapeutic and prognostic biomarkers for SRRC.

Using New Vaginal Doses Evaluation System to Assess the Dose-Effect Relationship for Vaginal Stenosis After Definitive Radio(Chemo)Therapy for Cervical Cancer.

Objective: The study aims to investigate if a relationship exists between vaginal doses and vaginal stenosis (VS) using posterior-inferior border of symphysis (PIBS) points and the International Commission on Radiation Units-Rectum (ICRU-R) point evaluation system for definitive radio(chemo)therapy in locally advanced cervical cancer. Methods and Materials: From a vaginal dose study in China, 351 patients were prospectively assessed. For every reference point of the PIBS system and ICRU-R point was calculated for all BT and summed with EBRT. Pearson's chi-square test and Student's unpaired t-test compared variables with and without vaginal stenosis (VS) G ≥2. The risk factors were assessed for VS G ≥2 in multi- and univariate analyses through Cox proportional hazards model followed by a dose-effect curve construction. The VS morbidity rate was compared via the log-rank test using the median vaginal reference length (VRL). Results: The patients (38-month median follow-up) had 21.3% three-year actuarial estimate for VS G ≥2. Compared to G <2 patients, VS G ≥2 patients received higher doses to PIBS points except for PIBS - 2 and had significantly shorter VRL. VRL (HR = 1.765, P = 0.038), total EBRT and BT ICRU-R point dose (HR = 1.017, p = 0.003) were risk factors for VS. With VRL >4.6 cm, the 3-year actuarial estimate was 12.8% vs. 29.6% for VRL ≤4.6 cm. According to the model curve, the risks were 21, 30, and 39% at 75, 85, and 95 Gy, respectively (ICRU-R point dose). Conclusions: PIBS system point doses correlated with late vaginal toxicity. VRL combined with both EBRT and BT dose to the ICRU-R point contribute to VS risk.

Perceptions of pelvic floor dysfunction and rehabilitation care amongst women in southeast China after radical hysterectomy: a qualitative study.

OBJECTIVE: To investigate the perceptions of pelvic floor dysfunction (PFD) and rehabilitation care amongst women after radical hysterectomy and to explore ways to improve quality of care. METHODS: Thirty-six women who underwent radical hysterectomy at a hospital in southeast China were enrolled via purposive sampling. Semi-structured in-depth interviews were conducted. The texts were analysed via qualitative content analysis. RESULTS: Four themes were obtained: serious lack of knowledge, heavy psychological burden, different coping strategies and great eagerness to receive multiparty support on PFD rehabilitation care. CONCLUSION: The society and professional staff should strengthen health education on PFD. Professionals should offer education before and after surgery and actively provide rehabilitation consultation to promote the availability of rehabilitation to support women with PFD rehabilitation care. In addition, family-centred care is an important way to support women to return to normal life, and women's need for family support should be more actively expressed. Moreover, knowledge of medical insurance should be popularised, especially in rural areas in China.

MG53 represses high glucose-induced inflammation and angiogenesis in human retinal endothelial cells by repressing the EGR1/STAT3 axis.

BACKGROUND: Diabetic retinopathy (DR) is a vascular complication of diabetes mellitus that leads to visual injury and blindness. Both angiogenesis and inflammation play an important role in the pathogenesis of DR. Here we aimed to explore the mechanisms of mitsugumin 53 (MG53) in ameliorating the dysfunction induced by high glucose (HG) in humans retinal microvascular endothelial cells (HRECs). METHODS: HRECs were subjected to HG in the presence or absence of MG53 overexpression. The effect of MG53 on cell viability and inflammatory response in HG-treated HRECs was measured using the Cell Counting Kit-8 and ELISAs, respectively. Expression of MG53, EGR1, p-STAT3, FGF2, TGFB1, and Angiopoietin-1 in HG-treated HRECs was quantified by western blot or quantitative real-time polymerase chain reaction. RESULTS: HG significantly downregulated MG53 in HRECs, which reduced cell viability while inducing angiogenesis and inflammatory response. Upregulation of MG53 reversed these effects of HG. MG53 directly interacted with EGR1 and repressed its expression, which decreased phosphorylation of STAT3 and downregulated FGF2, TGFB1, and Angiopoietin-1. EGR1 up-regulation or STAT3 activation antagonized the protective effects of MG53. CONCLUSION: MG53 alleviates HG-induced dysfunction in HRECs by repressing EGR1/STAT3 signaling. Thereby MG53 may have therapeutic potential in DR.

Identifying the hub gene and immune infiltration of Parkinson's disease using bioinformatical methods.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that affects 1%-2% of the population over 60 years old. Immune response dysfunction in the brain contributes to the occurrence and development of PD. This study aimed to uncover the potential diagnostic genes for PD and characterize the immune cell infiltrates. METHODS: We downloaded the microarray data of patients with PD samples from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the modules linked to PD in the GSE20163 dataset. Meanwhile, differentially expressed genes (DEGs) between the healthy control samples and PD samples were also identified. Then the PD-related genes were integrated based on the genes in the key module and DEGs. Functional enrichment analysis was used to explore the molecular mechanisms of these PD-related genes. Protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) analysis were used to further screen candidate genes for PD. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of these candidate genes. The infiltration of immune cells was detected by single-sample gene set enrichment analysis (ssGSEA) algorithm in the GSE20163 dataset, and Pearson analysis was used to investigate the correlation of candidate genes with immune cells and immune checkpoint proteins. The expression of candidate genes in clinical samples was verified by qPCR. RESULTS: Altogether, we found a unique gene module related to PD, where 109 DEGs were identified in the GSE20163 dataset. Following these results, we screened 68 genes associated with PD. Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that these genes were markedly enriched in the pathway of synthesis and transport of neurons. Three candidate genes (SLC18A2, CALB1, and SYNGR3) were further identified in PD patients through PPI network and LASSO analysis. The receiver operating characteristic (ROC) curve indicated that the three candidate genes had a good performance in distinguishing the PD samples from healthy control samples. The proportions of the aDC, DC, NK CD56dim cells, and follicular helper T cells (TFH) were obviously different between the healthy control and PD samples. Moreover, CTLA4, LAG3, CEACAM1, and CD27 were highly expressed in the PD group. GSEA analysis for candidate genes revealed that they were all closely related to the neurogenic disease. Additionally, the three candidate genes were all strongly correlated with the above immune cells and immune checkpoint proteins. The qPCR results validated the expression differences of SLC18A2 and SYNGR3 in the clinical PD and control samples. CONCLUSION: The three candidate genes may be a useful tool for diagnosing PD patients. These findings provide a reference for exploring new therapeutic targets and strategies for PD treatment.

Natural bioactive constituents from herbs and nutraceuticals promote browning of white adipose tissue.

Obesity is a significant public health problem worldwide that is characterized by abnormal or excessive fat accumulation. Unfortunately, the application of available weight-loss drugs has been restricted because of their serious adverse effects. Browning of white adipose tissue (WAT), which refers to the transformation of white adipocytes to beige adipocytes under certain stimulations, is regarded as a new strategy to solve the obesity problem. Numerous studies have recently evidenced that traditional Chinese medicine (TCM) could promote browning of WAT with multi-component and multi-target characteristics. This article summarizes natural constituents from TCM with stimulatory effects on browning of WAT in the past two decades. The active ingredients can be generally divided into polyphenols, saponins, alkaloids, terpenoids, phenylpropanoids and others, such as resveratrol, quercetin, curcumin, genistein, capsaicin, epigallocatechin gallate (EGCG), berberine, menthol, emodin and ginsenosides. Simultaneously, the chemical structures, source, model, efficacy and mechanism of these monomeric compounds are also described. And the mechanisms of these active ingredients are mainly involved in the regulation of PRDM16, PGC-1α, PPARγ, SIRT1, AMPK, ß3-adrenergic receptors, TRPV1 and TRPM8 channels, FGF21 and miRNAs. The present article opens opportunities for developing novel drugs or supplements from TCM with wide acceptability to prevent obesity progression and its associated metabolic disorders.

MiRNA-122 Promotes Ischemia-Reperfusion Injury after Lung Transplantation via the Toll-like Receptor Signaling Pathway.

OBJECTIVE: MiRNAs have been recently implicated in the pathogenesis of ischemia-reperfusion (IR) injury. This study aimed to investigate the miRNA expression profiles in the early stages after lung transplantation (LT) and to study the involvement of the Toll-like receptor (TLR) signaling pathway in lung IR injury following LT. METHODS: We established the left LT model in mice and selected the miRNA-122 as a research target. The mice were injected with a miRNA-122-specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing of transplanted lung tissues to identify differentially expressed (DE) miRNAs and their target genes. These target genes were used to further perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: A total of 12 DE miRNAs were selected, and 2476 target genes were identified. The GO enrichment analysis predicted 6063 terms, and the KEGG analysis predicted 1554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung wet/dry ratio (P<0.05). In addition, the activity of myeloperoxidase and the expression levels of tumor necrosis factor-alpha and TLR2/4 were decreased (P<0.05); whereas the expression of interleukin-10 was increased (P<0.05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway. CONCLUSION: Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.

[Hsa_circ_0005221 promotes prostate cancer progression through the miR-339-5p/STAT5a pathway].

OBJECTIVE: To investigate the molecular mechanism of hsa_circ_0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway. METHODS: Localizations of hsa_circ_0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa_circ_0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa_circ_0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa_circ_0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis. RESULTS: The expression of hsa_circ_0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa_circ_0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa_circ_0005221, which was just the reverse in those with overexpressed hsa_circ_0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa_circ_0005221, with most obvious changes in miR-339-5p when hsa_circ_0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa_circ_0005221 to miR-339-5p. Knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa_circ_0005221 and transfection of miR-339-5p mimics induced just the opposite effects. CONCLUSIONS: Hsa_circ_0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.