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Although there have been recent advances in the molecular pathology of ependymomas, little is known about the underlying molecular evolution during its development. Here, we assessed the clinical, pathological and molecular evolutionary process of ependymoma recurrence in a 9-year-old patient who had seven recurrences of supratentorial ependymoma and died from intracranial multiregional recurrences at the age of 19 years old. Whole-genome sequencing (WGS) of 7 tumor samples (1 primary and 6 subsequent recurrent tumors) was performed to elucidate the mutation landscape and identify potential driver mutations for tumor evolution. The genetic profiles of the seven tumor specimens showed significant heterogeneity and suggested a highly branched evolutionary pattern. The mutational signatures and chromothripsis changed with treatments. Strikingly, adhesion G protein-coupled receptor L3 (ADGRL3, also known as Latrophilins 3, LPNH3) was found to be consistently mutated during the entire disease process. However, Sanger sequencing of other 78 ependymoma patients who underwent surgery at our institution showed no genetic alteration of ADGRL3, as found in the present case. The mRNA levels of ADGRL3 were significantly lower in ependymomas (n = 36), as compared with normal brain tissue (n = 3). Grade III ependymomas had the lowest ADGRL3 expression. Moreover, ependymomas with lower mRNA level of ADGRL3 had shorter overall survival. Our findings, therefore, demonstrate a rare evolutionary process of ependymoma involving ADGRL3.

Background Acute kidney injury (AKI) is a common and severe complication of cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to establish a model to predict the probability of postoperative AKI in patients undergoing cardiac surgery with CPB. Methods We conducted a retrospective, multicenter study to analyze 1082 patients undergoing cardiac surgery under CPB. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the AKI model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the previously mentioned model. Finally, we used multiple methods to evaluate the accuracy and clinical applicability of the model. Results Age, gender, hypertension, CPB duration, intraoperative 5% bicarbonate solution and red blood cell transfusion, urine volume were identified as important factors. Then, these risk factors were created into nomogram to predict the incidence of AKI after cardiac surgery under CPB. Conclusion We developed a nomogram to predict the incidence of AKI after cardiac surgery. This model can be used as a reference tool for evaluating early medical intervention to prevent postoperative AKI.

Microneedle fractional radiofrequency (MFR) and non-ablative 1565 nm fractional laser (NAFL) have recently been introduced as new techniques to address the growing concern of facial photoaging. In this prospective randomized split-face study, we wanted to compare the safety and efficacy of MFR with that of NAFL for the treatment of facial photoaging in Asian patients. Fifteen healthy Chinese patients were enrolled for this randomized split-face study. Each patient underwent three sessions of treatment with MFR and NAFL on opposite sides of their face, one month apart. A blinded outcome assessment of the photoaging severity was performed by two independent plastic surgeons on a 5-point visual analogue scale (VAS, 0-4). Patient satisfaction was also scored based on a 5-point VAS (0 = dissatisfaction, 4 = extremely satisfied). Sagging of the nasolabial groove was evaluated using the Antera 3D camera, facial wrinkles and pores using the VISIA skin analysis system. Any adverse events that occurred during the study were also evaluated. Based on the VAS scores and results from the Antera 3D and VISIA, it was noted that there was a significant improvement in facial skin laxity, wrinkles, and pores, and lesser sagging of the nasolabial groove on both the MFR and NAFL sides of the face, compared with that of the baseline. Most patients were satisfied with the treatment and reported tolerable pain and crusting. Although no significant differences were observed between the MFR and NAFL treatments, the NAFL treatment resulted in a shorter downtime(4.56 ± 2.72d) than the MFR treatment(6.96 ± 3.27d). This study confirms the efficacy of MFR and NAFL treatments for facial skin rejuvenation in Asian patients. Furthermore, the therapies were found to be safe and well-tolerated. Our findings suggest that NAFL may be a more convenient treatment modality for facial photoaging because of its shorter downtime. However, sagging of the nasolabial groove was more improved by the MFR treatment than by the NAFL treatment.

Context The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5-10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation. Objective To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT. Methods A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post-SIT. These patients then underwent the CCT where PACs post-CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver-operator characteristic curves (AUC), sensitivity and specificity were calculated. Results There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true-positive numbers increased from 134 to 147, and false-negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P = .041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P = .028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post-CCT resulted in a 36% higher AUC than using PAC post-SIT alone for the diagnosis of PA. Conclusion For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy.

Aim: We aimed to identify that long noncoding RNAs (lncRNAs) are involved in ischemia-reperfusion (IR)-induced late fibrosis of kidney and may constitute novel therapeutic strategies for acute kidney injury-induced chronic kidney disease. Materials & methods: We performed the mouse model of IR later induced renal fibrosis and analyzed lncRNA profiles using second-generation sequencing during the pathogenesis. Results: The expression levels of 43 lncRNAs and 141 lncRNAs were respectively changed significantly 7 days and 2 weeks after IR treatment. Based on the correlation analysis of the differentially expressed genes, the interaction networks of lncRNAs, miRNAs and mRNA were structured. Conclusion: LncRNA (Gm12840) could act as a sponge for miR-677-5p to mediate fibroblast activation induced by TGF-β1 via the WISP1/PKB (Akt) signaling pathway.

Neuropathic pain (NP) can occur after peripheral nerve injury (PNI), and it can be converted into a maladaptive, detrimental phenotype that causes a long-term state of pain hypersensitivity. In the last decade, the discovery that dysfunctional microglia evoke pain, called "microgliopathic pain," has challenged traditional neuronal views of "pain" and has been extensively explored. Recent studies have shown that microRNAs (miRNAs) can act as activators or inhibitors of spinal microglia in NP conditions. We first briefly review spinal microglial activation in NP. We then comprehensively describe miRNA expression changes and their potential mechanisms in the response of microglia to nerve injury. We summarize the roles of the following two representative miRNAs: miR-124, which reverses NP by keeping microglia quiescent, and miR-155, which promotes NP following microglial activation. Finally, we focused on the therapeutic potential of microglial miRNAs in NP. The findings we summarized may be essential tools for basic research and clinical treatment of NP.

Programmed cell death-1 (PD-1) belongs to an inhibitory signaling pathway capable of maintaining central and peripheral immune tolerance. Blockage of PD-1 has been identified as a promising immunotherapeutic approach for cancer and chronic infectious diseases. However, it is unknown whether PD-1 pathway regulates stem cell function. It is generally believed that mesenchymal stem cells (MSCs) produce PD-1 ligand, but fail to express PD-1. In this study, we show that neural crest-derived MSCs from dental pulp (MSC-DP), but not MSCs from bone marrow, expressed PD-1. Knocking down PD-1 expression in MSC-DP results in a significantly reduced capacity for cell proliferation and accelerated multipotential differentiation. Mechanistically, we show that PD-1 regulates a SHP2/ERK/Notch cascade to maintain proliferation and a SHP2/ERK/β-catenin cascade to inhibit osteo-/odontogenic differentiation. This study indicates that PD-1 is a key surface molecule controlling cell proliferation and multipotential differentiation of MSC-DP. Through regulating PD-1/SHP2/ERK signaling, we can significantly improve the quality and quantity of culture-expanded MSC-DP for potential clinical therapies.

Electronic health records contain patient's information that can be used for health analytics tasks such as disease detection, disease progression prediction, patient profiling, etc. Traditional machine learning or deep learning methods treat EHR entities as individual features, and no relationships between them are taken into consideration. We propose to evaluate the relationships between EHR features and map them into Procedures, Prescriptions, and Diagnoses (PPD) tensor data, which can be formatted as images. The mapped images are then fed into deep convolutional networks for local pattern and feature learning. We add this relationship-learning part as a boosting module on a commonly used classical machine learning model. Experiments were performed on a Chronic Lymphocytic Leukemia dataset for treatment initiation prediction. Experimental results show that the proposed approach has better real world modeling performance than the baseline models in terms of prediction precision.

Renal fibrosis is an inevitable consequence of parenchymal scarring and is the common final pathway that mediates almost all progressive renal diseases. Adiponectin, a hormone produced by adipose tissue, possesses potent anti-insulin, anti-inflammatory, and anti-fibrotic properties. Reportedly, adiponectin serves as an important messenger that facilitates complex interactions between adipose tissue and other metabolically related organs. In recent years, a growing body of evidence supports adiponectin involvement in renal fibrosis. These studies provide a deeper understanding of the molecular mechanism of action of adiponectin in renal fibrosis and also offer a potential preventive and therapeutic target for renal fibrosis. In this review, the physiological role of adiponectin is briefly introduced, and then the mechanism of adiponectin-mediated renal fibrosis and the related signaling pathways are described. Finally, we summarize the findings regarding the clinical value of adiponectin in renal fibrotic diseases and prospected its application potential.

As a particularly important mediator of intercellular communication, extracellular vesicles (EVs) have been proved to be extensively involved in various system diseases over the past two decades, including in renal diseases. As is well-known, renal fibrosis is the common pathological process of any ongoing renal disease or adaptive repair of kidney injury based on current knowledge. Although much work has been performed focusing on EVs in various renal diseases, the role of EVs in renal fibrosis has not been described in detail and summarized. In this review, we provide a brief overview of the definition, classification and biological process of EVs. Then, the potential mechanisms of EVs in renal fibrosis are illustrated. Lastly, recent advances in EVs and the implications of EVs for diagnosis and therapy in renal fibrosis disease are introduced. We look forward to a more comprehensive understanding of EVs in renal fibrosis, which could be a boon to patients with renal fibrosis disease.

Fibrosis is the final common pathological feature of a wide variety of chronic kidney disease (CKD). However, an understanding of the mechanisms underlying the development of renal fibrosis remains challenging and controversial. As the current focus of molecular research, noncoding RNAs (ncRNAs), mainly microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular noncoding RNAs (circRNAs), have powerful and abundant biological functions, which essentially makes them mediators of the physiological and pathological processes of various system diseases. The role of ncRNAs in renal fibrosis has also received great attention in recent years, but most research has mainly focused on miRNAs. In fact, although a large number of studies of lncRNAs have emerged recently, the role these molecules play in renal fibrosis haven't been fully understood till now. Thus, this review discusses the discovery of lncRNAs and their biological functions in different types of renal fibrosis, as well as the imminent applications of these findings in clinical use. Undoubtedly, in the future, further understanding of the function of all types of lncRNAs will reveal large breakthroughs in the treatment of renal fibrosis.

Neuropathic pain (NP) is ranked as one of the major forms of chronic pain and emerges as a direct consequence of a lesion or disease affecting the somatosensory nervous system. Despite great advances into the mechanisms of NP, clinical practice is still not satisfactory. Fortunately, progress in elucidating unique features and multiple molecular mechanisms of long non-coding RNAs (lncRNAs) in NP has emerged in the past 10 years, suggesting that novel therapeutic strategies for pain treatment may be proposed. In this review, we will concentrate on recent studies associated with lncRNAs in NP. First, we will describe the alterations of lncRNA expression after spinal cord injury (SCI) and peripheral nerve injury (PNI), and then we illustrate the role of some specific lncRNAs in detail, which may offer new insights into our understanding of the etiology and pathophysiology of NP. Finally, we put special emphasis on the altered expression of lncRNAs in the diverse biological process of NP. Recent advances we summarized above in the development of NP may facilitate translation of these findings from bench to bedside in the future.

Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy.

Objective To determine the effects of a cleft deformity unilateral cleft lip and palate (UCLP) and the subsequent surgical interventions on maxillary growth. Materials and methods This retrospective study evaluated the lateral cephalograms of 3 groups of individuals: 40 adult patients with ULCP who underwent surgery for both lip and palate; 40 adult patients with ULCP who underwent surgery for lip only; and 40 age- and gender-matched noncleft controls. Differences in jaw morphology among them were analyzed statistically. Results Adult UCLP patients in both groups showed maxillary hypoplasia in anteroposterior and vertical directions compared with noncleft control adults. Significant differences ( p ≤ 0.01) in the ANB (subspinale–nasion–supramentale angle), NA-FH (the angle formed between Frankfort horizontal plane and the plane from nasion to subspinale), MP-FH (the angle formed between mandibular plane and Frankfort horizontal plane), and GoMe/SN (the ratio between length of mandibular body and length of anterior cranial base) were found between the two UCLP patient groups. Although maxillary growth in the two UCLP groups was less than that in the noncleft control group, the anteroposterior growth in the UCLP patients with palatoplasty was even less than that in the UCLP patients with unoperated palate. Conclusions There may be an intrinsic deficiency of maxillary anteroposterior and vertical development in UCLP patients compared with the noncleft controls. Palatoplasty can further limit the anteroposterior growth of maxilla but has no detrimental effect on maxillary vertical development. The mandible is rotated clockwise after palatoplasty in UCLP patients.

FOXF2 (forkhead box F2) is a mesenchyme-specific transcription factor that plays a critical role in tissue homeostasis through the maintenance of epithelial polarity. In a previous study, we demonstrated that FOXF2 is specifically expressed in basal-like breast cancer (BLBC) cells and functions as an epithelial-mesenchymal transition suppressor. FOXF2 deficiency enhances the metastatic ability of BLBC cells through activation of the epithelial-mesenchymal transition program, but reduces cell proliferation. In this study, we demonstrate that CpG island methylation of the FOXF2 proximal promoter region is involved in the regulatory mechanism of the subtype-specific expression of FOXF2 in breast cancer cells. DNMT1, DNMT3A, and DNMT3B commonly or individually contributed to this DNA methylation in different breast cancer cells. SP1 regulated the transcriptional activity of FOXF2 through direct binding to the proximal promoter region, whereas this binding was abrogated through DNA methylation. FOXF2 mediated the SP1-regulated suppression of progression and promotion of proliferation of non-methylated BLBC cells. Thus, we conclude that the subtype-specific expression and function of FOXF2 in breast cancer cells are regulated through the combined effects of DNA methylation and SP1 transcriptional regulation.

Molecular medical research on aromatherapy has been steadily increasing for use as an adjuvant therapy in managing psychiatric disorders and to examine its therapeutic mechanisms. Most studies, as well as clinically applied experience, have indicated that various essential oils, such as lavender, lemon and bergamot can help to relieve stress, anxiety, depression and other mood disorders. Most notably, inhalation of essential oils can communicate signals to the olfactory system and stimulate the brain to exert neurotransmitters (e.g. serotonin and dopamine) thereby further regulating mood. However, little research has been done on the molecular mechanisms underlying these effects, thus their mechanism of action remains ambiguous. Several hypotheses have been proposed regarding the therapeutic mechanism of depression. These have mainly centered on possible deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP, cation channels as well as neuroimmune interactions and epigenetics, however the precise mechanism or mechanisms related to depression have yet to be elucidated. In the current study, the effectiveness of aromatherapy for alleviating psychiatric disorders was examined using data collected from previously published studies and our unpublished data. A possible signaling pathway from olfactory system to the central nerve system and the associated key molecular elements of aromatherapy are also proposed.

Myc-associated zinc finger protein (MAZ) is a transcription factor with C2H2-type zinc-finger motifs that can bind GC-rich cis-elements. MAZ activates the transcription of some cancer-related genes and represses that of others, suggesting that changes in MAZ expression may play different roles in the development and progression of different types or subtypes of cancers depending on its target genes. However, the functions and mechanisms of MAZ in regulating the carcinogenesis and progression of breast cancer have remained unclear. In the current study, we show that MAZ performs dual function in basal-like breast cancer (BLBC): suppression of aggressiveness and promotion of proliferation. Forkhead box F2 (FOXF2) is a novel transcription target of MAZ and mediates the functions of MAZ. The MAZ mRNA level, particularly in combination with the FOXF2 mRNA level, may serve as a prognostic marker for BLBC patients. Our results indicate that the dual function of the MAZ-FOXF2 axis reflect the pleiotropic nature of multifunctional transcription factors in regulating the different stages of cancer development and progression, which could lead to the complexity of cancer diagnosis and treatment.

Decline of antioxidant defense after estrogen deficiency leads to oxidative damage in bone marrow-derived mesenchymal stem cells (BMMSCs), resulting a defect of bone formation in osteoporosis. Forkhead box O1 (FoxO1) protein is crucial for defending physiological oxidative damage in bone. But whether FoxO1 is involved in the oxidative damage during osteoporosis is largely unknown. In this study, we found that FoxO1 protein accumulation was decreased in BMMSCs of ovariectomized mice. The decrease of FoxO1 resulted in the suppression of manganese superoxide dismutase (Sod2) and catalase (Cat) expression and accumulation of reactive oxygen species (ROS), inhibiting the osteogenic differentiation of BMMSCs. The decline of FoxO1 protein was caused by tumor necrosis factor-alpha (TNF-α) accumulated after estrogen deficiency. Mechanistically, TNF-α activated NF-κB pathway to promote microRNA-705 expression, which function as a repressor of FoxO1 through post-transcriptional regulation. Inhibition of NF-κB pathway or knockdown of miR-705 largely prevented the decline of FoxO1-mediated antioxidant defense caused by TNF-α and ameliorated the oxidative damage in osteoporotic BMMSCs. Moreover, the accumulated ROS further activated NF-κB pathway with TNF-α, which formed a feed-forward loop to persistently inhibiting FoxO1 protein accumulation in BMMSCs. In conclusion, our study revealed that the decline of FoxO1 is an important etiology factor of osteoporosis and unclosed a novel mechanism of FoxO1 regulation by TNF-α. These findings suggested a close correlation between inflammation and oxidative stress in stem cell dysfunction during degenerative bone diseases.

To explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor.Totally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung.Buzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P0.05), but without statistical difference compared with the blank control group.Among nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.

Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from regulating calcium homeostasis and bone function, its levels also associate with the presence of development of adenocarcinoma. VitD can interact with VitD receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then induces transcription of proteins that function in cell proliferation, differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes and their associated polymorphisms involved in the correlation between development of adenocarcinoma and VitD deficiency to highlight how VitD may be instrumental in cancerization. Furthermore, pilot epidemiological data show that the detection of 25-hydroxy-Vitamin D3 ((36.5±10.7 nmol/L, n=129) vs (81.4±19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this review, we suggest that 25-hydroxy-Vitamin D3 can act as an indicator and/or risk assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma.

Fenvalerate (FEN) has been demonstrated to be a reproductive toxicant in humans and rodents. However, little is known about whether short-term exposure to low-dose FEN produces reproductive toxicity.We administered FEN (0.009 375, 0.1875, 3.750, or 45.00 mg×kg(-1)×d(-1) by gavage for 30 days) to male ICR mice and compared reproductive toxicity parameters between groups receiving different concentrations of FEN. Reproductive toxicity was evaluated by computer-assisted semen quality analysis (CASA), chlortetracycline (CTC) assay, and histopathology.The sperm morphology and testis histology of FEN-exposed mice (all doses) were similar to that in controlling mice. Exposure to FEN at a concentration of 0.1875 mg×kg(-1)×d(-1) decreased sperm path straightness (STR) and linearity (LIN) (both P0.05), but had no significant impact on average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), lateral amplitude (ALH), beat cross frequency (BCF), or progressive motility (MOT). FEN reduced the rate of mouse sperm capacitation in a dose-dependent manner.The present results demonstrate that exposure to low-dose FEN for 30 days reduces semen quality and sperm capacitation in adult mice.

Early diagnosis and treatment of ulcerative colitis (UC) is clinically challenging. To overcome this problem, we explored the interrelated multiplex signaling pathway to identify molecular signatures in UC by using integrated strategy in proteomics. Intestinal mucosa of 12 UC cases and 12 normal controls underwent comparative proteomic analysis. A total of 26 unique differential proteins were identified, including 12 up-regulated and 14 down-regulated in UC group. A differential protein cluster, consisting of 11 proteins involved in p38 mitogen-activated protein kinase (MAPK) pathway, was deduced and validated by Western blot. Furthermore, three proteins elicited from the protein cluster, phosphorylated p38, MAWBP and galectin-3, as a molecular signature, were analyzed by immunohistochemistry on 118 UC and normal samples. Increased expression of P-p38 and down-regulated MAWBP and/or galectin-3 were detected in UC compared to normal samples (p < 0.001). This signature correlated with disease progression of UC (p < 0.01), and classified UC risk with high sensitivity (94.83 ± 2.91%) and specificity (98.33 ± 1.65%). In addition, P38 MAPK pathway modulated the expression of the protein clusters in macrophage cell line as evidenced by the alteration with specific inhibitor SB203580. These results indicate that molecular signature of P38 MAPK pathway might be a potential biomarker for evaluating UC risk.

To explore the biomarkers of early diagnosis in patients with polycyclic aromatic hydrocarbons (PAHs)-related lung cancer for the application to detection of occupational lung cancer or related lung cancer.Western dot blotting was used to explore the expression of ras, p53 and heat stress protein 70 (HSP70) in 29 patients with PAHs-related lung cancer (LC), and 28 patients with non-cancerous pulmonary disease, and 30 healthy controls.The positive detection rates of P21, P53, and HSP70 in LC group (58.62%, 34.48%, 41.38% respectively) were higher than those in non-cancerous pulmonary disease group (14.29%, 7.14%, 10.71% respectively, P0.01). The sensitivity of P21, P53 and HSP70 were 58.62%, 34.48% and 41.38% respectively, negative predictive value (NPV) were 68.42%, 78.05% and 63.04% respectively. The co-detection of the three proteins mentioned above produced a sensitivity of 82.76% with a NPV of 78.26% (P0.05). Of 18 cases of LC with negative cytology, 13 (72.22%) were found HSP21, P53 or HSP70 positive.Co-detection of the P21, P53, and HSP70 may be used as the screening marker for diagnosis of PAHs-related lung cancer, and may supplement the diagnostic value of conventional cytology.

Background The cause of almost all cases of Parkinson’s disease (PD) remains unknown. Recent years have seen an explosion in the rate of discovery of genetic defects linked to PD. Different racial and geographical populations may have different distributions of genetic variants. Methods In the current study, we screened the following genetic variants, including some rare mutations and single nucleotide polymorphisms (SNPs), in a pedigree and cases-controls. To best of our knowledge, we first screened these variants known to be associated with neurodegeneration disease, E46K (rs104893875) in SNCA, A1442P in LRRK2, IVS9 in PARK2, A350V in SLC41A1, P268S (rs2066842), R702W (rs2066844), G908R (rs2066845), 1007fs (rs2066847) in NOD2 and G2385R (rs34778348) in LRRK2 from southern China population. Genotyping was performed by jointly using primers overlapping polymerase chain reaction (PCR) site-directed mutagenesis, restriction fragment length polymorphism (RFLP), and capillary electrophoresis (CE). Results We didn’t discover above 9 variants in the family members of the pedigree. Furthermore, of 237 patients with sporadic Parkinson’s disease and 190 controls, no heterozygosity or homozygosity were found from E46K, A1442P, A350V, R702W, G908R, or 1007fs but heterozygosity onto G2385R, IVS9, and P268S. No significant difference between cases and controls was found in both allele frequency (P = 0.572) and genotype frequency (P = 0.348) of IVS9. However, significant differences in genotype frequency (P = 0.009) of G2385R were consistent with prior observation. Eight patients with Parkinson’s disease (2 women and 6 men are over the age of 50 years at onset of PD) carried the P268S heterozygous variation in NOD2. There was no heterozygosity or homozygosity of P268S in the controls. Genotype frequency of P268S (P = 0.0450) had significant differences. Conclusions Our results suggested that the P268S variant in NOD2 might be a risk factor for susceptibility to sporadic Parkinson’s disease in Chinese populations. It also implied that the inflammatory response may play a role in PD.

Background The histopathological and molecular heterogeneity of normal tissue adjacent to cancerous tissue (NTAC) and normal tissue adjacent to benign tissue (NTAB), and the availability of limited specimens make deciphering the mechanisms of carcinogenesis challenging. Our goal was to identify histogenetic biomarkers that could be reliably used to define a transforming fingerprint using RNA in situ hybridization. Methods We evaluated 15 tumor-related RNA in situ hybridization biomarkers using tumor microarray and samples of seven tumor-adjacent normal tissues from 314 patients. Biomarkers were determined using comprehensive statistical methods (significance of support vector machine-based artificial intelligence and area under curve scoring of classification distribution). Results TP53 was found to be a most reliable index (P -7; area under curve >87%) for distinguishing NTAC from NTAB, according to the results of a significance panel (BCL10, BECN1, BRCA2, FITH, PTCH11 and TP53). Conclusions The genetic alterations in TP53 between NTAC and NTAB may provide new insight into the field of cancerization and tumor transformation.