Navigating the Evolving Landscape of Primary Hyperoxaluria: Traditional Management Defied by the Rise of Novel Molecular Drugs.

Primary hyperoxalurias (PHs) are inherited metabolic disorders marked by enzymatic cascade disruption, leading to excessive oxalate production that is subsequently excreted in the urine. Calcium oxalate deposition in the renal tubules and interstitium triggers renal injury, precipitating systemic oxalate build-up and subsequent secondary organ impairment. Recent explorations of novel therapeutic strategies have challenged and necessitated the reassessment of established management frameworks. The execution of diverse clinical trials across various medication classes has provided new insights and knowledge. With the evolution of PH treatments reaching a new milestone, prompt and accurate diagnosis is increasingly critical. Developing early, effective management and treatment plans is essential to improve the long-term quality of life for PH patients.

Gastric and cardiac inflammatory myofibroblastic tumor: an extremely rare case.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient's stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun's gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review. CONCLUSIONS: As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.

MICA: a multi-omics method to predict gene regulatory networks in early human embryos.

Recent advances in single-cell omics have transformed characterisation of cell types in challenging-to-study biological contexts. In contexts with limited single-cell samples, such as the early human embryo inference of transcription factor-gene regulatory network (GRN) interactions is especially difficult. Here, we assessed application of different linear or non-linear GRN predictions to single-cell simulated and human embryo transcriptome datasets. We also compared how expression normalisation impacts on GRN predictions, finding that transcripts per million reads outperformed alternative methods. GRN inferences were more reproducible using a non-linear method based on mutual information (MI) applied to single-cell transcriptome datasets refined with chromatin accessibility (CA) (called MICA), compared with alternative network prediction methods tested. MICA captures complex non-monotonic dependencies and feedback loops. Using MICA, we generated the first GRN inferences in early human development. MICA predicted co-localisation of the AP-1 transcription factor subunit proto-oncogene JUND and the TFAP2C transcription factor AP-2γ in early human embryos. Overall, our comparative analysis of GRN prediction methods defines a pipeline that can be applied to single-cell multi-omics datasets in especially challenging contexts to infer interactions between transcription factor expression and target gene regulation.

Impact of bariatric surgery on glucose and lipid metabolism and liver and kidney function in food-induced obese diabetic rats.

BACKGROUND: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. AIM: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats. METHODS: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted. RESULTS: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C ß/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups. CONCLUSION: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM.

The effects of chemotherapy, primary tumor location and histological subtype on the survival of stage III colon cancer patients.

OBJECTIVE: Colon cancer (CC) is one of the most common cancers worldwide and has a poor prognosis. Surgery followed by adjuvant chemotherapy is the standard treatment strategy for stage III CC patients. Primary tumor location (PTL) is an important factor for the long-term survival of CC. However, the difference in the prognosis between the histological subtypes of mucinous adenocarcinoma (MAC) and nonspecific adenocarcinoma (AC) in stage III CC patients is unclear. The correlation of chemotherapy, PTL and histological subtype with the overall survival (OS) of stage III CC patients has not yet been explored. METHODS: Patients diagnosed with stage III CC from 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and OS were analyzed according to the chemotherapy, PTL and histological subtype. RESULTS: A total of 28,765 eligible stage III CC patients were enrolled in this study. The results showed that chemotherapy, left-sided CC (LCC) and AC were favorable prognostic factors for OS. Right-sided CC (RCC) had worse OS than LCC regardless of chemotherapy. MAC had worse OS than AC in the patients with chemotherapy, but the survival benefits disappeared in the patients without chemotherapy. Additionally, in LCC, MAC had worse OS than AC regardless of chemotherapy. However, in RCC, MAC had worse OS than AC in patients with chemotherapy but had similar OS to AC in patients without chemotherapy. In the AC group, RCC had worse OS than LCC regardless of chemotherapy. In the MAC group, RCC had comparable OS to LCC regardless of chemotherapy. Four subgroups, i.e., RCC/MAC, RCC/AC, LCC/MAC and LCC/AC, all showed benefits from chemotherapy. Among them, LCC/AC had the best OS, and RCC/MAC had the worst OS compared with the other three subgroups. CONCLUSION: The prognosis of MAC is worse than that of AC in stage III CC. LCC/AC has the best OS, while RCC/MAC has the worst OS but still benefits from chemotherapy. The impact of chemotherapy on survival is greater than that of histological subtype, but the impact of histological subtype on survival is similar to that of PTL.

Dynamic analysis of a new aquatic ecological model based on physical and ecological integrated control.

Within the framework of physical and ecological integrated control of cyanobacteria bloom, because the outbreak of cyanobacteria bloom can form cyanobacteria clustering phenomenon, so a new aquatic ecological model with clustering behavior is proposed to describe the dynamic relationship between cyanobacteria and potential grazers. The biggest advantage of the model is that it depicts physical spraying treatment technology into the existence pattern of cyanobacteria, then integrates the physical and ecological integrated control with the aggregation of cyanobacteria. Mathematical theory works mainly investigate some key threshold conditions to induce Transcritical bifurcation and Hopf bifurcation of the model (2.1), which can force cyanobacteria and potential grazers to form steady-state coexistence mode and periodic oscillation coexistence mode respectively. Numerical simulation works not only explore the influence of clustering on the dynamic relationship between cyanobacteria and potential grazers, but also dynamically show the evolution process of Transcritical bifurcation and Hopf bifurcation, which can be clearly seen that the density of cyanobacteria decreases gradually with the evolution of bifurcation dynamics. Furthermore, it should be worth explaining that the most important role of physical spraying treatment technology can break up clumps of cyanobacteria in the process of controlling cyanobacteria bloom, but cannot change the dynamic essential characteristics of cyanobacteria and potential grazers represented by the model (2.1), this result implies that the physical spraying treatment technology cannot fundamentally eliminate cyanobacteria bloom. In a word, it is hoped that the results of this paper can provide some theoretical support for the physical and ecological integrated control of cyanobacteria bloom.

Development and validation of a prognostic nomogram for patients with stage II colon mucinous adenocarcinoma.

PURPOSE: Mucinous histology is generally considered as a risk factor of prognosis in stage II colon cancer, but there is no appropriate model for prognostic evaluation and treatment decision in patients with stage II colon mucinous adenocarcinoma (C-MAC) Thus, it is urgent to develop a comprehensive, individualized evaluation tool to reflect the heterogeneity of stage II C-MAC. METHODS: Patients with stage II C-MAC who underwent surgical treatment in the Surveillance, Epidemiology, and End Results Program were enrolled and randomly divided into training cohort (70%) and internal validation cohort (30%). Prognostic predictors which were determined by univariate and multivariate analysis in the training cohort were included in the nomogram. The calibration curves, decision curve analysis, X-tile analysis, and Kaplan-Meier curve of the nomogram were validated in the internal validation cohort. RESULTS: Three thousand seven hundred sixty-two patients of stage II C-MAC were enrolled. The age, pathological T (pT) stage, tumor number, serum carcinoembryonic antigen (CEA), and perineural invasion (PNI) were independent predictors of overall survival (OS), which were used to establish a nomogram. Calibration curves of the nomogram indicated good consistency between nomogram prediction and actual survival for 1-, 3- and 5-year OS. Besides, patients with stage II C-MAC could be divided into high-, middle-, and low-risk subgroups by the nomogram. Further subgroup analysis indicated that patients in the high-risk group could have a survival benefit from chemotherapy after surgical treatment. CONCLUSIONS: We established the first nomogram to accurately predict the survival of stage II C-MAC patients who underwent surgical treatment. In addition, the nomogram identified low-, middle-, and high-risk subgroups of patients and found chemotherapy might improve survival in the high-risk subgroup of stage II C-MAC patients.

Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis.

PURPOSE: Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy. METHODS: Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963-August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI). RESULTS: This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I2 = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups. CONCLUSION: MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.

LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection.

Persistent infection of Chlamydia trachomatis is thought to be responsible for the debilitating sequelae of blinding trachoma and infertility. Inhibition of host cell apoptosis is a persistent C. trachomatis infection mechanism. ZEB1-AS1 is a long non-coding RNA (lncRNA), which was up-regulated in persistent C. trachomatis infection in our previous work. In this study, we investigated the role of ZEB1-AS1 in persistent infection and the potential mechanisms. The results showed that ZEB1-AS1 was involved in the regulation of apoptosis, and targeted silencing of ZEB1-AS1 could increase the apoptosis rate of persistently infected cells. Mechanically, interference ZEB1-AS1 caused an apparent down-regulation of the Bcl-2/Bax ratio and the repression of the mitochondrial membrane potential with the remarkable release of cytochrome c, resulting in the significant elevation level of caspase-3 activation. Meanwhile, the luciferase reporter assay confirmed that ZEB1-AS1 acted as a sponge for miR-1224-5p to target MAP4K4. The regulatory effect of miR-1224-5p/MAP4K4 on persistent infection-induced antiapoptosis was regulated by ZEB1-AS1. In addition, ZEB1-AS1 inhibited the apoptosis of Chlamydia-infected cells by activating the MAPK/ERK pathway. In conclusion, we found a new molecular mechanism that the ZEB1-AS1/miR-1224-5p/MAP4K4 axis contributes to apoptosis resistance in persistent C. trachomatis infection. This work may help understand the pathogenic mechanisms of persistent C. trachomatis infection and reveal a potential therapeutic strategy for its treatment.

Effectiveness of bone substitute materials in opening wedge high tibial osteotomy: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis of eligible studies was performed to evaluate the effectiveness of bone substitute materials (BSMs) in opening wedge high tibial osteotomy (OWHTO) for knee osteoarthritis. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A comprehensive literature search was performed, and studies comparing BSM with bone graft (BG) and without bone graft (WG) were included. The Cochrane risk of bias tool (version 1.0) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool were used to assess the risk of bias for randomized controlled trials (RCTs) and non-randomized studies (NRSs), respectively. The outcomes measured were the osteotomy gap size, the occurrence rates of non-union and lateral hinge fractures, knee functional score, infection and the Visual Analogue Scale (VAS). The quality of evidences was evaluated by Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system. RESULTS: Five RCTs and eight NRS including 769 participants were included in our meta-analysis. The BSM group had a larger osteotomy gap size than the control group (MD: 0.41 mm, 95% confidence interval (CI): [0.06, 0.76], p=.02, I2=0%), with a significant difference. No significant difference was found between BSM and control group in main analysis in terms of bone non-union, but with a higher non-union rate when BSM combined with long locking plate was used. No significant differences were found in other outcome measures except for VAS from NRS subgroup. The quality of evidence for outcomes was low. CONCLUSIONS: BSM combined with locking plate techniques offers a safe and efficient alternative option in OWHTO for osteotomy gap larger than 10 mm, but be aware of the possibility of bone non-union. Given the inherent heterogeneity and low quality of the included studies, future well-designed RCTs are essential to verify the findings.KEY MESSAGEThe treatment of the osteotomy gap is still controversial.BSM combined with a locking plate offers a safe and efficient alternative option for OWHTO with an over 10 mm of osteotomy gap over 10 mm.Due to the inherent heterogeneity and low quality of the included studies, the results should be cautiously interpreted in clinical practice.

Perineural Versus Intravenous Dexamethasone for Brachial Plexus Block: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Perineural (PN) dexamethasone (DEX) administration can prolong the analgesic time of a brachial plexus block. However, its efficacy and safety are controversial due to its off-label use and different routes of administration. OBJECTIVES: This meta-analysis aimed to assess the safety and efficacy of PN versus intravenous (IV) dexamethasone. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). SETTING: Relevant studies were found through a comprehensive literature search of PubMed, Web of Science, Ovid, EMBASE, and the Cochrane Library (from the inception until January 2020). METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this meta-analysis was conducted to identify RCTs comparing PN and IV dexamethasone in brachial plexus block. A randomized effect model was used in the meta-analysis and the subgroup analysis was performed with adrenaline stratification. The quality of evidence and the strength of recommendations were graded by GradePro version 3.6.1. RESULTS: Twelve RCTs with a total of 1,345 subjects were included. We found that PN dexamethasone could prolong the duration of analgesia (mean difference [MD]: 131.82 minutes, 95% confidence interval [CI] [38.96, 224.68], I2 = 82%, P = 0.005), motor block (MD: 218.85 minutes, 95% CI [113.65,324.05], I2 = 72%, P < 0.0001) and sensory block (MD: 209.57 minutes, 95% CI [72.64, 346.50], I2 = 87%, P = 0.003) in the main analysis with significant difference. In the absence of epinephrine, there were no significant differences between PN dexamethasone and IV dexamethasone. Except for adverse-effects, no significant differences were observed in secondary outcomes. PN dexamethasone had slightly higher adverse-effects; however, these could be altered if a sensitivity analysis was conducted. LIMITATIONS: There was high heterogeneity among included studies. CONCLUSIONS: PN dexamethasone can prolong the duration of analgesia, sensory block, and motor block, when compared with IV dexamethasone. In a subgroup analysis without epinephrine, the 2 routes of administration were equivalent to topical anesthesia. There were no differences in secondary outcomes, except for adverse effects, which could be altered if a sensitivity analysis was conducted. Therefore, despite the advantages of PN dexamethasone, caution is needed due to its off-label character. While the results of this study are promising, additional large and well-designed RCTs are needed to validate these initial findings and their implications.

Endoscopy biopsy is not efficiency enough for diagnosis of mucinous colorectal adenocarcinoma.

BACKGROUND: Endoscopy biopsy (EB) is the standard diagnostic method for colorectal cancer (CRC), whereas its accuracy and efficiency in mucinous adenocarcinoma (MAC) initial diagnosis is unclear. METHODS: The initial EB and postoperative specimen (PS) pathological diagnosis of MAC from two centers were retrospectively collected and analyzed. The accuracy and efficiency of initial EB compared with PS pathological diagnosis were analyzed. The potential factors which would affect the initial EB diagnosis of MAC were analyzed. RESULTS: 280 and 78 eligible cases were enrolled in this study from two centers respectively. The initial EB diagnosis accuracy for MAC were 84.62% and 83.33%. However, among the cases of PS diagnosis with MAC, the diagnostic efficiency of initial EB was only 36.49% and 32.50% respectively. Lower tumor differentiation and more EB number were associated with an increased probability for the EB diagnosis of MAC, but only tumor differentiation was an independent diagnositic factor for EB in the two cohorts. CONCLUSIONS: The accuracy of initial EB with MAC is high, but the diagnostic efficiency was extremely low. Tumor differentiation and EB number were associated with the diagnosis efficiency of MAC before surgery.

Surgery improves the prognosis of colon mucinous adenocarcinoma with liver metastases: a SEER-based study.

BACKGROUND: Mucinous adenocarcinoma (MC) is the second most common pathological type of colon carcinoma (CC). Colon cancer liver metastases (CLMs) are common and lethal, and complete resection of the primary tumour and metastases for CLM patients would be beneficial. However, there is still no consensus on the role of surgery for MC with liver metastases (M-CLM). METHODS: Patients diagnosed with M-CLM or classical adenocarcinoma with CLM (A-CLM) from 2010 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The clinicopathological features and overall survival (OS) and cancer-specific survival (CSS) data were compared and analysed. RESULTS: The results showed that the M-CLM group had a larger tumour size, more right colon localizations, higher pT and pN stages, more female patients, and more retrieved and positive lymph nodes and accounted for a higher proportion of surgeries than the A-CLM group. The OS and CSS of M-CLM patients who underwent any type of surgery were significantly better than those of patients who did not undergo any surgery, but poorer than those of A-CLM patients who underwent surgery. Meanwhile, the OS and CSS of M-CLM and A-CLM patients who did not undergo any surgery were comparable. Compared with hemicolectomy, partial colectomy led to similar or better OS and CSS for M-CLM, and surgery was an independent protective factor for long-term survival in M-CLM. CONCLUSIONS: M-CLM had distinct clinicopathological characteristics from A-CLM, and surgery could improve the survival and is an independent favourable prognostic factor for M-CLM. In addition, partial colectomy might be a non-inferiority choice as hemicolectomy for M-CLM according to the results from this study.

Retroperitoneal teratoma misdiagnosed as a gastric stromal tumor: A case report.

The misdiagnosis of retroperitoneal teratoma as a gastric stromal tumor is rarely reported. There are numerous abdominal organs, and retroperitoneal tumors are easily concealed by organs situated more anteriorly on the abdomen; therefore, retroperitoneal tumors are easily misdiagnosed as human digestive system tumors by abdominal surgeons. We herein present the case of a 39-year-old female patient who was diagnosed with a gastric stromal tumor (GST) on preoperative examination, whereas the postoperative diagnosis was retroperitoneal mature cystic teratoma. Such cases are clinically rare. In the present case, the tumor was located in the retroperitoneum, near the lesser gastric curvature, without an obvious gap. The anterior surface of the tumor was concealed by the lesser gastric curvature and did not move significantly with breathing and changes in posture. In such cases, a preoperative misdiagnosis is very likely. The aim of the present study was to improve our understanding of the presentation of retroperitoneal teratomas, thereby gaining more clinical experience and hopefully reducing the rate of misdiagnosis.

Hemicolectomy Does Not Provide Survival Benefit for Right-Sided Mucinous Colon Adenocarcinoma.

BACKGROUND: The extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC. METHODS: Patients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed. RESULTS: A total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall survival (OS) of the MAC group was poorer than that of the AC group, but cancer-specific survival (CSS) was similar between the two groups. The RHC subgroup of the MAC group had more patients of age ≤60 years, larger tumor size, cecum/ascending colon location and dissected lymph nodes than the PC subgroup, but similar positive lymph nodes, perioperative mortality, OS and CSS as the PC subgroup. Moreover, the univariate and multivariable analyses for the survival of RCC patients with MAC showed that RHC might not be a superior predictor for OS and CSS compared with PC. CONCLUSIONS: RHC could not dissect more positive lymph nodes or provide long-term survival benefits for RCC patients with MAC compared with PC. This study could provide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.

Chlamydia trachomatis Plasmid Protein pORF5 Up-Regulates ZFAS1 to Promote Host Cell Survival via MAPK/p38 Pathway.

Long non-coding RNAs (lncRNAs) have been demonstrated to play essential roles in many diseases. However, few studies have shown that lncRNAs take part in the pathogenesis of Chlamydia trachomatis (C. trachomatis). Here, we used a lncRNA microarray to detect the global lncRNA expression profiles in HeLa cells transfected with pORF5 plasmid protein, an important virulence factor for C. trachomatis. The differentially expressed lncRNAs and mRNAs screened by microarray were selected for validation by quantitative real-time PCR. The up-regulated lncRNA zinc finger antisense 1 (ZFAS1) was presumed to involved in MAPK pathways by bioinformatics analysis. Inhibition of ZFAS1 decreased the apoptotic rate of pORF5 and reduced the infectivity of C. trachomatis, and MAPK/p38 pathway was involved in anti-apoptotic effect induced by ZFAS1. Therefore, the present study confirmed that pORF5 up-regulates ZFAS1 to promote host cell survival via MAPK/p38 pathway and influences the infectivity of C. trachomatis.

ZNF382: A transcription inhibitor down-regulated in multiple tumors due to promoter methylation.

Zinc finger protein 382 (ZNF382), a member of the Krüppel-associated box zinc finger proteins (KRAB-ZFPs) family, plays critical roles in regulating certain downstream genes expression as a transcription inhibitor. ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter, to be more specific, methylation of promoter CpG island may contributes to inhibition of gene expression as found in many studies. With application of DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2'-deoxycytidine, hypomethylation of ZNF382 gene may contribute to anti-tumor effects. This review summerized the structure, biological functions, expression and the roles of ZNF382 in multiple cancers, and, expression of ZNF382 regulated by promoter methylation was further discussed to show the possibilities of DNA hypomethylation treatment as a potential treatment in clinical applications.

Chlamydia trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis via the PI3K-AKT-mediated MDM2-p53 axis.

Chlamydia trachomatis, the most common human pathogen that causes trachoma and sexually transmitted disease, has developed various strategies for inhibiting host cell apoptosis. Activation of the PI3K (phosphoinositide 3-kinase)/AKT-mediated MDM2 (murine double minute 2)-p53 pathway plays a prominent role in the apoptosis resistance arising from C. trachomatis infection. However, the precise upstream mechanisms by which C. trachomatis activates this pathway have not been adequately investigated. Here, we reveal that the secreted C. trachomatis plasmid-encoded protein Pgp3 inhibits apoptosis in HeLa cells. This process requires the activation of the PI3K/AKT signaling pathway, thereby leading to phosphorylation and nuclear entry of MDM2, and p53 degradation. PI3 K inhibitor LY294002 and MDM2 inhibitor Nutlin-3a block Pgp3-induced inhibition of HeLa cell apoptosis, suggesting a critical role for the PI3K/AKT pathway and its effect on the MDM2-p53 axis in Pgp3 anti-apoptotic activity.

Identification of proteins interacting with pORF5 in the pathogenesis of C. trachomatis.

OBJECTIVE: This study is to identify and investigate the proteins interacting with pORF5 implicated in the pathogenesis of C. trachomatis. METHODS: The isobaric tags for relative and absolute quantitation (iTRAQ) approach combined with nano liquid chromatography-tandem mass spectrometry (NanoLC-MS/MS) analysis was applied to identify and quantify the differentially expressed proteins in the pORF5-transfected HeLa (pORF5-HeLa) cells and the control vector-transfected HeLa (vector-HeLa) cells. Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to detect the mRNA and protein expression levels. RESULTS: Totally 3355 proteins were quantified by employing biological replicates, 314 of which were differentially expressed between the pORF5-HeLa and vector-HeLa cells. Nine differentially expressed proteins (HIST1H1C, HBA1, PARK7, HMGB1, HMGB2, CLIC1, KRT7, SFN, and CDKN2A) were subjected to qRT-PCR, and two over-expressed proteins (HMGB1 and PRAK7) were subjected to the Western blot analysis, to validate the proteomic results. The results from the qRT-PCR and Western blot analysis were consistent with the findings from the proteomic analysis. Moreover, pORF5 could inhibit the TNF-α-induced apoptosis in HeLa cells. Through siRNA-mediated functional screening, the high-mobility group box 1 (HMGB1) was shown to be relevant to the inhibition of the apoptotic response in the host cells. CONCLUSION: Identification of key proteins interacting with pORF5 could contribute to the understanding and further exploration of the function of pORF5 in the pathogenic mechanisms of C. trachomatis.