Air pollution, greenspace exposure and risk of Parkinson's disease: a prospective study of 441,462 participants.

BACKGROUND: The current understandings of the relationship between air pollution (AP), greenspace exposure and Parkinson's Disease (PD) remain inconclusive. METHODS: We engaged 441,462 participants from the UK Biobank who were not diagnosed with PD. Utilizing Cox proportional hazard regression model, relationships between AP [nitrogen dioxide (NO2), and nitrogen oxides (NOX), particulate matter < 2.5 µm in aerodynamic diameter(PM2.5), coarse particulate matter between 2.5 µm and 10 µm in aerodynamic diameter(PM2.5-10), particulate matter < 10 µm in aerodynamic diameter(PM10)], greenspace exposure, and PD risk were determined independently. Our analyses comprised three models, adjusted for covariates, and affirmed through six sensitivity analyses to bolster the robustness of our findings. Moreover, mediation analysis was deployed to discern the mediating effect of AP between greenspaces and PD. RESULTS: During a median follow-up of 12.23 years (5,574,293 person-years), there were 3,293 PD events. Each interquartile (IQR) increment in NO2 and PM10 concentrations were associated with 10% and 8% increase in PD onset risk, while the increases in NOX, PM2.5 and PM2.5-10 were not associated with PD risk. Additionally, greenspace may safeguard by reducing NO2 and PM10 levels, with the effect mediated by NO2 and PM10 in greenspace-PD relationship. CONCLUSION: Our findings indicate that an IQR increase in ambient NO2 and PM10 concentrations was associated with risk of PD development, while other pollutants (NOX, PM2.5 and PM2.5-10) were not associated with PD risk. Firstly, we find that augmented exposure to greenspace was associated with the lower PD risk by reducing NO2 and PM10 levels.

Encapsulation of Lactobacillus plantarum in W1/O/W2 double emulsions stabilized with the high-intensity ultrasound-treated pea protein and pectin.

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion's viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.

The roles and mechanisms of SREBP1 in cancer development and drug response.

Cancer occurrence and development are closely related to increased lipid production and glucose consumption. Lipids are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition, signal transduction, and energy supply, which are vital for cancer cell rapid proliferation, invasion, and metastasis. Sterol regulatory element-binding transcription factor 1 (SREBP1) is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis, lipid homeostasis, and fatty acid synthesis. In addition, SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases, particularly cancer. However, no review of SREBP1 in cancer biology has yet been published. Herein, we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells, including SREBP1 modification, lipid metabolism and reprogramming, glucose and mitochondrial metabolism, immunity, and tumor microenvironment, epithelial-mesenchymal transition, cell cycle, apoptosis, and ferroptosis. Additionally, we discussed the potential role of SREBP1 in cancer prognosis, drug response such as drug sensitivity to chemotherapy and radiotherapy, and the potential drugs targeting SREBP1 and its corresponding pathway, elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

In Vivo Transcranial Acoustoelectric Brain Imaging of Different Deep Brain Stimulation Currents.

Deep brain stimulation (DBS) is an effective treatment for neurologic disease and its clinical effect is highly dependent on the DBS leads localization and current stimulating state. However, standard human brain imaging modalities could not provide direct feedback on DBS currents spatial distribution and dynamic changes. Acoustoelectric brain imaging (AEBI) is an emerging neuroimaging method that can directly map current density distribution. Here, we investigate in vivo AEBI of different DBS currents to explore the potential of DBS visualization using AEBI. According to the typical DBS stimulus parameters, four types of DBS currents, including time pattern, waveform, frequency, and amplitude are designed to implement AEBI experiments in living rat brains. Based on acoustoelectric (AE) signals, the AEBI images of each type DBS current are explored and the resolution is quantitatively analyzed for performance evaluation. Furtherly, the AE signals are decoded to characterize DBS currents from multiple perspectives, including time-frequency domain, spatial distribution, and amplitude comparation. The results show that in vivo transcranial AEBI can accurately locate the DBS contact position with a millimeter spatial resolution (< 2 mm) and millisecond temporal resolution (< 10 ms). Besides, the decoded AE signal at DBS contact position is capable of describing the corresponding DBS current characteristics and identifying current pattern changes. This study first validates that AEBI can localize in vivo DBS contact and characterize different DBS currents. AEBI is expected to develop into a noninvasive DBS real-time monitoring technology with high spatiotemporal resolution.

The roles and mechanism of m6A RNA methylation regulators in cancer immunity.

N6-methyladenosine (m6A), the most common internal modification in RNA, can be regulated by three types of regulators, including methyltransferases (writers), demethylases (erasers), and m6A binding proteins (readers). Recently, immunotherapy represented by immune checkpoint blocking has increasingly become an effective cancer treatment, and increasing shreds of evidence show that m6A RNA methylation affects cancer immunity in various cancers. Until now, there have been few reviews about the role and mechanism of m6A modification in cancer immunity. Here, we first summarized the regulation of m6A regulators on the expression of target messenger RNAs (mRNA) and their corresponding roles in inflammation, immunity response, immune process and immunotherapy in various cancer cells. Meanwhile, we described the roles and mechanisms of m6A RNA modification in tumor microenvironment and immune response by affecting the stability of non-coding RNA (ncRNA). Moreover, we also discussed the m6A regulators or its target RNAs which might be used as predictor of cancer diagnosis and prognosis, and shed light on the potentiality of m6A methylation regulators as therapeutic targets in cancer immunity.

M6AREG: m6A-centered regulation of disease development and drug response.

As the most prevalent internal modification in eukaryotic RNAs, N6-methyladenosine (m6A) has been discovered to play an essential role in cellular proliferation, metabolic homeostasis, embryonic development, etc. With the rapid accumulation of research interest in m6A, its crucial roles in the regulations of disease development and drug response are gaining more and more attention. Thus, a database offering such valuable data on m6A-centered regulation is greatly needed; however, no such database is as yet available. Herein, a new database named 'M6AREG' is developed to (i) systematically cover, for the first time, data on the effects of m6A-centered regulation on both disease development and drug response, (ii) explicitly describe the molecular mechanism underlying each type of regulation and (iii) fully reference the collected data by cross-linking to existing databases. Since the accumulated data are valuable for researchers in diverse disciplines (such as pathology and pathophysiology, clinical laboratory diagnostics, medicinal biochemistry and drug design), M6AREG is expected to have many implications for the future conduct of m6A-based regulation studies. It is currently accessible by all users at: https://idrblab.org/m6areg/.

TKIs combined with chemotherapy followed by allo-HSCT in Philadelphia chromosome-positive myelodysplastic syndrome: A case report and literature review.

INTRODUCTION: Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature. PATIENT CONCERNS AND DIAGNOSIS: We report a 38-year-old woman with Ph-positive MDS. INTERVENTIONS AND OUTCOMES: She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed. CONCLUSION: Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.

Low energy harvesting of hydrophobic microalgae (Tribonema sp.) by electro-flotation without coagulation.

Microalgae have great potential for biofuel production and wastewater treatment, but the high cost of harvesting hinders their practical application. In this study, economical harvesting of hydrophobic microalgae by electro-flotation without coagulation was assessed. The harvesting performance of this method for selected species of freshwater microalgae with different degrees of hydrophobicity (Tribonema sp., highly hydrophobic; Scenedesmus sp., moderately hydrophobic; and Pandorina sp., hydrophilic) were compared. It was found that microalgal hydrophobicity played a critical role in electro-flotation. Under the same condition (current 0.3 A, velocity gradient 200 s-1, biomass concentration 1 g/L), Tribonema sp. could be effectively harvested (96.2 ± 0.4%) after 20 min of electro-flotation, while the harvesting efficiency decreased significantly with Scenedesmus sp. (70.1 ± 5.2%, 20 min) and Pandorina sp. (<10%, 1 h). The influences of current, electrolysis time, mixing intensity (velocity gradient) and biomass concentration on Tribonema sp. (hydrophobic) harvesting were further investigated. Increasing the current within a certain range (0.1 A-0.4 A) was beneficial to harvesting, while it's further increase decreased floating velocity, which was similar to the effect of the velocity gradient. Under the optimal condition, the harvesting efficiency of Tribonema sp. was 96.3% and the energy consumption (0.19 kWh/kg biomass) was much lower than other harvesting techniques, indicating that electro-flotation is a time-saving and economical approach for hydrophobic microalgae harvesting.

The Biological Functions and Regulatory Mechanisms of Fatty Acid Binding Protein 5 in Various Diseases.

In recent years, fatty acid binding protein 5 (FABP5), also known as fatty acid transporter, has been widely researched with the help of modern genetic technology. Emerging evidence suggests its critical role in regulating lipid transport, homeostasis, and metabolism. Its involvement in the pathogenesis of various diseases such as metabolic syndrome, skin diseases, cancer, and neurological diseases is the key to understanding the true nature of the protein. This makes FABP5 be a promising component for numerous clinical applications. This review has summarized the most recent advances in the research of FABP5 in modulating cellular processes, providing an in-depth analysis of the protein's biological properties, biological functions, and mechanisms involved in various diseases. In addition, we have discussed the possibility of using FABP5 as a new diagnostic biomarker and therapeutic target for human diseases, shedding light on challenges facing future research.

Melatonin Inhibits 17ß-Estradiol-Induced Epithelial-Mesenchymal Transition in Endometrial Adenocarcinoma Cells via Upregulating Numb Expression.

OBJECTIVES: Melatonin (MLT) shows antitumor effects in various tumor types, including endometrial carcinoma. However, the molecular mechanism involved is unclear. In the current study, we investigated the effect of MLT on the estrogen-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells and explored the pathway that might be involved. DESIGN: Laboratory study was via cultured endometrial cancer cells. Design refers only to in vitro experiments. METHODS: In cell culture experiments, cell growth was examined using CCK-8 assays. The expression of Numb and EMT markers in Ishikawa cells was examined using Western blot analysis and real-time PCR. Cell invasion was examined using transwell assays. Cell migration was examined using wound-healing assays and transwell assays. Using immunohistochemistry analysis, the expression of Numb in human endometrial cancers was examined. RESULTS: In immunohistochemistry experiments, we found that 15.2% of atypical endometrial hyperplasia and 15.6% of endometrial carcinoma did not express Numb. In cell culture experiments, MLT inhibited cell proliferation, invasion, and migration induced by 17ß-estradiol (E2) in endometrial cancer cells. MLT decreased the expression of vimentin and Slug and increased the expression of Numb and E-cadherin in Ishikawa cells. Numb knockdown in cancer cells significantly increased cell proliferation, invasion, and migration. LIMITATIONS: No animal experiments were performed. CONCLUSIONS: MLT blocked E2-induced cell growth and EMT in endometrial cancer cells via upregulating Numb expression.

ChREBP-regulated lipogenesis is not required for the thermogenesis of brown adipose tissue.

OBJECTIVES: Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis and represents an important therapeutic target for metabolic diseases. Carbohydrate response element-binding protein (ChREBP) is a key transcription factor regulating de novo lipogenesis, and its activity is associated with UCP1 expression and thermogenesis in BAT. However, the exact physiological role of endogenous ChREBP in BAT thermogenesis remains unclear. METHODS: We used the Cre/LoxP system to generate ChREBP BAT-specific knockout mice, and examined their BAT thermogenesis under acute cold exposure and long-term cold acclimation. Gene expression was analyzed at the mRNA and protein levels, and lipogenesis was examined by 3H-H2O incorporation assay. RESULTS: The mice lacking ChREBP specifically in BAT displayed a significant decrease in the expression levels of lipogenic genes and the activity of de novo lipogenesis in BAT after cold exposure, with UCP1 expression decreased under thermoneutral conditions or after acute cold exposure but not chronic cold acclimation. Unexpectedly, BAT-specific ChREBP deletion did not significantly affect body temperature as well as local temperature or morphology of BAT after acute cold exposure or chronic cold acclimation. Of note, ChREBP deletion mildly aggravated glucose intolerance induced by a high-fat diet. CONCLUSIONS: Our work indicates that ChREBP regulates de novo lipogenesis in BAT and glucose tolerance, but is not required for non-shivering thermogenesis by BAT under acute or long-term cold exposure.

Characterization of key aroma compounds in stewed mutton (goat meat) added with thyme (Thymus vulgaris L.) based on the combination of instrumental analysis and sensory verification.

Thyme (Thymus vulgaris L.) is widely used as a traditional spice in the cooking of goat meat (mutton) due to its distinctive flavor and the ability to weaken the "goaty flavor". To investigate the aroma characteristics of stewed mutton with thyme (SMT), four SMT samples prepared using different cooking utensils were analyzed by gas chromatography-mass spectrometry/olfactometry (GC-MS/O). Totally, 26 aroma-active compounds (AACs) were determined by GC-MS/O and further quantified. Among these, 20 AACs exhibited odor activity values (OAV) greater than 1. However, no significant differences existed among the four SMTs, which indicated that different utensils had little effect on the aroma profile of SMTs. Aroma recombination and omission experiments results showed that nonanal, (E)-2-octenal, and (E,E)-2,4-decadienal had the greatest contribution to the aroma profile of SMTs. These three compounds, together with dimethyl trisulfide, 3-methyl-butanal, octanal, (E)-2-decenal, (E)-2-nonenal, methanethiol, hexanal, (E)-2-undecenal, and 1-octen-3-ol, were confirmed as the key aroma compounds in SMTs.

Inhibitory effect of oil and fat on denitrification using food waste fermentation liquid as carbon source.

Food waste fermentation liquid (FWFL) can be used as carbon source to enhance nitrogen removal in wastewater treatment. However, the influence of lipid, a common component of food waste, on denitrification remains unclear. In this study, the effect of oil and fat on denitrification process and the underlying mechanisms were investigated using synthetic oil- and fat-bearing carbon source and verified with real FWFL. In the batch experiment, oil and fat had no obvious influence on denitrification, but in the semi-continuous experiment, the denitrification rate in the oil- and fat-added assays decreased to 44% and 38% of that in the control, respectively, after 45 batches. Oil and fat caused sludge floatation, and the floating sludge thickness increased with the continuous operation. Oil/fat-sludge aggregates were observed in the floating sludge and limited gas release. Microbial community analysis indicated that oil and fat did not affect denitrifying bacteria abundance. Limitation of mass transfer might be the main reason for the inhibition of oil and fat on denitrification. In the real FWFL experiment, the denitrification rate in the original and emulsified oil-bearing FWFL decreased to 24% and 56% of that in the demulsifying FWFL, respectively, after 45 batches. These findings indicate the necessity of removing lipids when FWFL is used as denitrification carbon source.

New framework for natural-artificial transport paths and hydrological connectivity analysis in an agriculture-intensive catchment.

The impacts of human activities on hydrological connectivity disturb the network topology of transport paths, which has gradually evolved from natural terrain features to dual natural-artificial features. In this study, a new framework is proposed to extract information from natural-artificial transport paths and related hydrological connectivity dominated by agricultural practices and ditch networks. Graph theory and connectivity indexes are integrated for the comprehensive classification and the parallel processing of potential flow transport networks and their upstream drainage areas. Based on high-resolution remote sensing data and detailed field investigations, this new framework, which combines graph theory and connectivity indexes, is applied to a typical agriculture-intensive catchment in China. The results show that artificial factors greatly influence the transport paths and the related drainage areas. With the development of ditch construction, the hydrological transport paths become shorter and more fragmented. In addition, key ditch segments are identified by connectivity indexes, and recommendations are given for future planning. This new framework offers an approach for the hydrological connectivity analysis of complex networks and provides effective strategies for agricultural development.

Fermentation liquid production of food wastes as carbon source for denitrification: Laboratory and full-scale investigation.

Nitrogen removal is often limited in municipal wastewater treatment due to the insufficiency of carbon source, and using food wastes fermentation liquid as carbon source could cut down the cost of operating and recycle food wastes. Food wastes fermentation liquid production and application as external carbon source were explored in the laboratory and full-scale system in this study. In the laboratory scale, lactic acid and VFAs were the main components of fermentation liquid, and the highest total chemical oxygen demand (TCOD) production was obtained with activated sludge as inoculum. The yield of TCOD was around 794.5 mg/g TSfed and NH4+-N was 3.5 mg/g TSfed. The denitrification rate with fermentation liquid was slightly lower than acetic acid and butyric acid, but higher than lactic acid and starch. In the full-scale investigation, the TCOD concentration in fermentation liquid was in the range of 6.9-12.8 g/L and the ratio of TCOD/inorganic nitrogen was 210.5-504.5:1. NO3--N removal increased from 52.1% to 94.2% after fermentation liquid addition, confirming the potentiality of food wastes fermentation liquid replace the commercial carbon source in wastewater treatment plants.

Biological functions of m6A methyltransferases.

M6A methyltransferases, acting as a writer in N6-methyladenosine, have attracted wide attention due to their dynamic regulation of life processes. In this review, we first briefly introduce the individual components of m6A methyltransferases and explain their close connections to each other. Then, we concentrate on the extensive biological functions of m6A methyltransferases, which include cell growth, nerve development, osteogenic differentiation, metabolism, cardiovascular system homeostasis, infection and immunity, and tumour progression. We summarize the currently unresolved problems in this research field and propose expectations for m6A methyltransferases as novel targets for preventive and curative strategies for disease treatment in the future.

ChREBP-ß regulates thermogenesis in brown adipose tissue.

Brown adipose tissue (BAT) plays a critical role in energy expenditure by uncoupling protein 1 (UCP1)-mediated thermogenesis. Carbohydrate response element-binding protein (ChREBP) is one of the key transcription factors regulating de novo lipogenesis (DNL). As a constitutively active form, ChREBP-ß is expressed at extremely low levels. Up to date, its functional relevance in BAT remains unclear. In this study, we show that ChREBP-ß inhibits BAT thermogenesis. BAT ChREBP-ß mRNA levels were elevated upon cold exposure, which prompted us to generate a mouse model overexpressing ChREBP-ß specifically in BAT using the Cre/LoxP approach. ChREBP-ß overexpression led to a whitening phenotype of BAT at room temperature, as evidenced by increased lipid droplet size and decreased mitochondrion content. Moreover, BAT thermogenesis was inhibited upon acute cold exposure, and its metabolic remodeling induced by long-term cold adaptation was significantly impaired by ChREBP-ß overexpression. Mechanistically, ChREBP-ß overexpression downregulated expression of genes involved in mitochondrial biogenesis, autophagy, and respiration. Furthermore, thermogenic gene expression (e.g. Dio2, UCP1) was markedly inhibited in BAT by the overexpressed ChREBP-ß. Put together, our work points to ChREBP-ß as a negative regulator of thermogenesis in brown adipocytes.

Cardiolipin remodeling by ALCAT1 links mitochondrial dysfunction to Parkinson's diseases.

Cardiolipin (CL) is a mitochondrial signature phospholipid that is required for membrane structure, respiration, dynamics, and mitophagy. Oxidative damage of CL by reactive oxygen species is implicated in the pathogenesis of Parkinson's disease (PD), but the underlying cause remains elusive. This work investigated the role of ALCAT1, an acyltransferase that catalyzes pathological remodeling of CL in various aging-related diseases, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP). We show that MPTP treatment caused oxidative stress, mtDNA mutations, and mitochondrial dysfunction in the midbrain. In contrast, ablation of the ALCAT1 gene or pharmacological inhibition of ALCAT1 prevented MPTP-induced neurotoxicity, apoptosis, and motor deficits. ALCAT1 deficiency also mitigated mitochondrial dysfunction by modulating DRP1 translocation to the mitochondria. Moreover, pharmacological inhibition of ALCAT1 significantly improved mitophagy by promoting the recruitment of Parkin to dysfunctional mitochondria. Finally, ALCAT1 expression was upregulated by MPTP and by α-synucleinopathy, a key hallmark of PD, whereas ALCAT1 deficiency prevented α-synuclein oligomerization and S-129 phosphorylation, implicating a key role of ALCAT1 in the etiology of mouse models of PD. Together, these findings identify ALCAT1 as a novel drug target for the treatment of PD.

NUMB knockdown enhanced the anti-tumor role of cisplatin on ovarian cancer cells by inhibiting cell proliferation and epithelial-mesenchymal transition.

BACKGROUND: NUMB is an inhibitory regulator of NOTCH signaling, which is critical for the induction of epithelial-mesenchymal transition (EMT). Loss of NUMB expression is correlated with the genesis and development of multiple tumors. Recent studies reported that NUMB expression was upregulated in human ovarian cancer. However, the role of NUMB in ovarian cancer is still unclear. Here, we invested the effect of NUMB knockdown on the proliferation and EMT in ovarian cancer cells and explored the role of NUMB in the effect of cisplatin. METHODS: Two ovarian cancer cells (OVCAR-3 and SK-OV-3) were used in the experiments. The proliferation and apoptosis of ovarian cancer cells was examined using methyl thiazolyl tetrazolium (MTT) test and flow cytometry assays. The invasion and migration of ovarian cancer cells were examined using Transwell assays. The expression of EMT markers were examined using Simple Western analysis. RESULTS: NUMB knockdown inhibited cell proliferation, invasion, and migration in both ovarian cancer cells. NUMB knockdown enhanced cisplatin-induced cell growth inhibiting and apoptosis in both ovarian cancer cells. NUMB knockdown enhanced cisplatin-induced cell invasion in SK-OV-3 cells. NUMB knockdown also decreased the expression of N-cadherin and Vimentin in SK-OV-3 cells. CONCLUSIONS: NUMB acted as an oncogene in ovarian cancer and NUMB knockdown enhanced the anti-tumor role of cisplatin on ovarian carcinoma cells by inhibiting cell proliferation and EMT.

Melatonin inhibits 17ß-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells.

BACKGROUND: Melatonin is a potential therapeutic agent for endometriosis, but its molecular mechanism is unclear. Here, we investigated the effect of melatonin on the epithelial-mesenchymal transition (EMT) in endometriotic endometrial epithelial cells and explored the pathway that might be involved. METHODS: This hospital-based study included 60 women of reproductive age using the endometrium for immunohistochemistry, 6 women of reproductive age undergoing bilateral tubal ligation and 6 patients with endometriosis for isolation of endometrial epithelial cells or subsequent analysis, respectively. We examined the expression of Notch1/Numb signaling and EMT markers by immunohistochemistry analysis and western blot analysis, the invasion and migration of endometrial epithelial cells by transwell assays, and the cell proliferation by CCK8 assays. RESULTS: Compared with normal endometrium, the endometriotic eutopic endometrium showed increased expression of Notch1, Slug, Snail, and N-cadherin, and decreased expression of E-cadherin and Numb. Melatonin or Notch inhibition by specific inhibitor blocked 17ß-estradiol-induced cell proliferation, invasion, migration and EMT-related markers in both normal and endometriotic epithelial cells. CONCLUSIONS: Our data suggest that aberrant expression of Notch1/Numb signaling and the EMT is present in endometriotic endometrium. Melatonin may block 17ß-estradiol-induced migration, invasion and EMT in normal and endometriotic epithelial cells by upregulating Numb expression and decreasing the activity of the Notch signaling pathway.