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Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital genitourinary abnormality defined by uterine didelphys, obstructed hemivagina, and ipsilateral urological anomalies. Accurate diagnosis and prompt commencement of therapy can be difficult owing to heterogeneous genitourinary malformation among different patients. This is a case report of a patient with rare HWWS with uterine didelphys, obstructed hemivagina, vagina-ureteral remnant fistula (Gartner's duct cyst), and ipsilateral kidney dysgenesis who complained of intermittent abdominal pain during menstruation. The right ureteral remnant of the patient was distinctive, with three portions. The upper section was connected to the right dysplastic kidney, the lower section formed the fistulous tract with the vagina and bladder, while the middle section communicated with Gartner's Duct Cyst, which merged with the vagina and opened to the posterior cavity of hemivagina. The lower section of the right ureter was excised and ligated during laparoscopic surgery, while the upper section was excised. The patient recovered after surgery. We presented this rare case and conducted a literature review to provide a more comprehensive understanding of HWWS. This could help gynecologists effectively reduce misdiagnosis and missed diagnosis, especially when combined with complicated urinary malformation.
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BACKGROUND: Neuroendocrine carcinoma (NEC) originating from the endometrium is rare, and there is limited knowledge regarding its diagnosis and optimal management. In this study, we present our experience with 11 patients with endometrial NEC, aiming to provide guidance for clinical practice. METHODS: We retrospectively collected the clinical, pathological, and treatment data of 11 patients with endometrial NEC who were treated at the First Affiliated Hospital of Zhengzhou University from January 2011 to July 2023. The clinicopathological characteristics, treatment and prognosis of these patients were analyzed. RESULTS: The median age of the patients was 55.0 (39.0-64.0) years, and the median tumor size was 40.0 (33.0-60.0) mm. Irregular vaginal bleeding was the most common symptom observed in 10 out of 11 patients, while metabolic syndrome occurred in only 2 out of 11 patients. Six out of the 11 patients were diagnosed at an early stage. Among the patients, 6 were diagnosed with endometrial NECs, while the remaining patients had a combination of endometrial NEC and other non-NEC endometrial carcinomas. All patients underwent surgery, except for one who received only chemotherapy due to multiple metastases. After surgery, adjuvant chemotherapy was administered to 5 patients, chemotherapy combined with radiotherapy was given to 3 patients, and 2 patients did not receive any adjuvant therapy. A total of 10 patients completed the follow-up, with a median follow-up time of 51.0 (14.3-81.0) months. Unfortunately, 2 patients died from the disease. CONCLUSION: NECs originating from the endometrium might not be affected by metabolic disorders. Preoperative diagnosis of these tumors was challenging. The primary approach for managing endometrial NEC can be multimodal treatment centered around surgery.
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Carcinoma Neuroendócrino , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/mortalidade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Prognóstico , Quimioterapia Adjuvante , Endométrio/patologia , Estadiamento de NeoplasiasRESUMO
Endometriosis is a disease characterized by the ectopic growth of endometrial tissue (glands and stroma) outside the confines of the uterus and often involves vital organs such as the intestines and urinary system. Endometriosis is considered a refractory disease owing to its enigmatic etiology, propensity for recurrence following conservative or surgical interventions, and the absence of radical treatment and long-term management. In recent years, the incidence of endometriosis has gradually increased, rendering it a pressing concern among women of childbearing age. A more profound understanding of its pathogenesis can significantly improve prognosis. Recent research endeavors have spotlighted the molecular mechanisms by which microRNAs (miRNAs) regulate the occurrence and progression of endometriosis. Many miRNAs have been reported to be aberrantly expressed in the affected tissues of both patients and animal models. These miRNAs actively participate in the regulation of inflammatory reactions, cellular proliferation, angiogenesis, and tissue remodeling. Their capacity to modulate crucial signaling pathways, such as the Wnt/ß-catenin signaling pathway, reinforces their potential utility as diagnostic markers or therapeutic agents for endometriosis. In this review, we provide the latest insights into the role of miRNAs that interact with the Wnt/ß-catenin pathway to regulate the biological behaviors of endometriosis cells and disease-related symptoms, such as pain and infertility. We hope that this review will provide novel insights and promising targets for innovative therapies addressing endometriosis.
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Endometriose , MicroRNAs , Animais , Humanos , Feminino , Endometriose/patologia , Via de Sinalização Wnt/fisiologia , Proliferação de Células , Modelos Animais de Doenças , beta Catenina/metabolismoRESUMO
BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and α-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of ß-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the ß-catenin/c-Myc/cyclin D1 pathway. CONCLUSION: This study reveals that porcine-derived AVM has potential application for vaginal regeneration.
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Transtornos 46, XX do Desenvolvimento Sexual , Anormalidades Congênitas , Ciclina D1 , Ductos Paramesonéfricos/anormalidades , Engenharia Tecidual , Humanos , Feminino , Suínos , Animais , beta Catenina , Porco Miniatura , Vagina/anormalidades , Vagina/cirurgiaRESUMO
Ovarian cancer is a highly heterogeneous and lethal malignancy with limited treatment options. Over the past decade, single-cell sequencing has emerged as an advanced biological technology capable of decoding the landscape of ovarian cancer at the single-cell resolution. It operates at the level of genes, transcriptomes, proteins, epigenomes, and metabolisms, providing detailed information that is distinct from bulk sequencing methods, which only offer average data for specific lesions. Single-cell sequencing technology provides detailed insights into the immune and molecular mechanisms underlying tumor occurrence, development, drug resistance, and immune escape. These insights can guide the development of innovative diagnostic markers, therapeutic strategies, and prognostic indicators. Overall, this review provides a comprehensive summary of the diverse applications of single-cell sequencing in ovarian cancer. It encompasses the identification and characterization of novel cell subpopulations, the elucidation of tumor heterogeneity, the investigation of the tumor microenvironment, the analysis of mechanisms underlying metastasis, and the integration of innovative approaches such as organoid models and multi-omics analysis.
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Neoplasias Ovarianas , Feminino , Humanos , Neoplasias Ovarianas/genética , Epigenoma , Multiômica , Organoides , Tecnologia , Microambiente Tumoral/genéticaRESUMO
Objective: The present study aimed to explore the feasibility and safety of robot-assisted total hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES). Methods: In this study, the clinical data of 37 patients who underwent da Vinci robot-assisted total hysterectomy by vNOTES between September 1, 2019 and March 31, 2022 at the Department of Gynecology, the First Affiliated Hospital of Zhengzhou University, China were retrospectively analyzed. Clinical characteristics, operative postoperative complications, surgical outcomes, and postoperative pain scores were collected and analyzed. Results: The average age of the patients included in the study was 47.43 ± 4.44 years. The body mass index (BMI) was calculated using the formula BMI = body weight (kg)/height2 (m2). The average BMI was 23.16 ± 2.72 kg/m2. Among the 37 patients, 30 patients underwent total hysterectomy and bilateral salpingectomy, of which 11 patients underwent ovarian cystectomy simultaneously. Among these 11 patients, three had bilateral ovarian cysts and eight had unilateral ovarian cysts, with the largest cyst diameter measuring 8 cm. The remaining seven patients underwent total hysterectomy and bilateral salpingo-oophorectomy. The average operative time was 86.19 ± 17.83 min, and the estimated intraoperative blood loss was 24.46 ± 15.40 mL, with no intraoperative complications reported. The time to the first postoperative exhaust was 18.51 ± 6.63 h, and the average postoperative length of hospital stay was 3.81 ± 1.05 days. The postoperative visual analog scale (VAS) pain scores were 5.30 ± 0.91 at 24 h after surgery, 3.30 ± 0.70 at 36 h after surgery, and 1.14 ± 0.92 at 48 h after surgery. Only one patient experienced a fever exceeding 38.5 °C, which resolved after receiving antibiotic treatment. Conclusion: The use of the da Vinci robot-assisted total hysterectomy by vNOTES demonstrated safety and offers several advantages. These include reduced surgical trauma, an aesthetic incision, decreased pain, and shorter duration of postoperative exhaust time and hospital stay. These benefits contribute to accelerated postoperative rehabilitation.
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Tissue engineering techniques bring the promise of vaginal reconstruction with low invasiveness and fewer complications. However, existing biomaterial scaffolds remain limited in efficient vaginal recovery, focusing only on regenerating an epithelial layer, but muscle layers are missing or abnormal. The lack of a multi-tissue hierarchical structure in the reconstructed vagina leads to shrinking, stenosis, and fibrosis. Here, an acellular matrix named a double-sided biomembrane (DBM) is demonstrated for vaginal recovery. The regeneration of epithelial and muscle layers is achieved simultaneously since the smooth side of the DBM is helpful for guiding epithelial cell growth, while its loose and porous side guides muscle cell growth. In addition, the DBM demonstrates excellent mechanical properties similar to vaginal tissue, and hydrophilicity. Therefore, neovaginas were observed in the fourth and twelfth weeks after DBMs were transplanted to repair full-thickness vaginal defects (4 cm) that we established in large animals. The DBMs can effectively promote rapid epithelialization, the formation of large muscle bundles, higher rates of angiogenesis, and the restoration of physiological function in a neovagina. That is, the injured vagina achieves nearly complete recovery in anatomy and function, similar to a normal vagina. These preclinical results indicate that the DBM has prospects for vaginal injury repair.
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Prolonging the reproductive lifespan is beneficial for preserving the physical and psychological health of women. The transplantation of mesenchymal stem cell (MSC)derived exosomes (MSCExos) has been reported to be a promising regenerative therapeutic strategy for restoring the function of aging ovaries. The present study thus evaluated the therapeutic efficacy of exosomes derived from human umbilical cordMSCs (hUCMSCExos) in a mouse model of natural ovarian aging (NOA), and further investigated the role of exosomal microRNAs (miRNAs/miRs) in the mechanisms of this creative therapy. Specifically, following the administration of hUCMSCExos in mice with NOA, ovarian function was found to improve, as indicated by the restoration of follicle numbers and hormone levels. These exosomes were found to exhibit the ability to inhibit PTEN expression and suppress apoptosis both in vivo and in vitro. Subsequently, miRNA sequencing of the exosomes was performed, following which bioinformatics analysis was used to identify the highly expressed miRNAs that are capable of targeting PTEN expression. Through highthroughput sequencing and molecular analyses, miR215p was found to be the highest in ranking in terms of expression, suggesting that hUCMSCExos can preserve ovarian function by suppressing PTEN expression to inhibit apoptosis by delivering miR215p. On the whole, the results of the present study suggest that the application of exosomes can be used to restore ovarian function in mice with NOA. These positive findings also suggest that the transplantation of exosomes derived from MSCs holds promise as an agent against ovarian aging.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Humanos , Feminino , Animais , Camundongos , MicroRNAs/genética , Envelhecimento , Apoptose , Fatores ImunológicosRESUMO
Endometrial cancer (EC) ranks as the sixth most common malignancy in women around the world. Although lowgrade and earlystage EC commonly have an excellent prognosis, ~20% of EC patients experience an unfavorable prognosis. Identifying the pathogenesis and novel therapeutic targets may help address this group of patients. Noncoding (nc)RNAs, such as long noncoding RNAs (lncRNAs), microRNAs and circular RNAs (circRNAs), have been associated with EC occurrence and development. In addition, the aberrant activation of the Wnt/ßcatenin signaling pathway can promote the proliferation, invasion, migration and epithelialtomesenchymal transition (EMT) of EC cells. The network of ncRNAs has also been demonstrated to inhibit or activate the Wnt/ßcatenin signaling pathway. In the present review, ncRNAs, the Wnt/ßcatenin signaling pathway, and their crosstalk in EC were summarized and highlighted. This information is expected to provide novel insights into improving the management of EC using RNA as therapeutics.
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Neoplasias do Endométrio , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Via de Sinalização Wnt/genética , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Endométrio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Gallbladder neuroendocrine carcinoma (GB-NEC) is a rare, aggressive neuroendocrine carcinoma that arises from the gallbladder. Patients with GB-NEC usually have a poor prognosis. The present study described two cases diagnosed with GB-NEC and reviewed the literature to improve knowledge of GB-NEC. The present study reported on two cases of GB-NEC in male patients aged 65 and 66 years, respectively. Both patients underwent surgical resection. Postoperative pathology confirmed that one case had mixed adeno-neuroendocrine carcinoma and the other had large cell neuroendocrine carcinoma. In addition, both patients had uneventful recoveries following surgery and received cisplatin-etoposide combination chemotherapy. The present study summarized the two cases and reviewed the literature to improve understanding of GB-NEC. The results revealed that radiological findings of GB-NEC are non-specific. The present study demonstrated that surgical resection was still the most effective therapy and that postoperative adjuvant chemotherapy could markedly improve the prognosis of patients with GB-NEC.
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Vaginal reconstruction has incorporated the use of gastrointestinal segments for decades, but the technique is inevitably associated with complications. Tissue-engineering techniques, however, have brought great hope for vaginal reconstruction. This study aimed to evaluate the utility of small intestinal submucosa (SIS) in reconstructing clinically significant large vaginal defects in a porcine model and to investigate the role of the Hippo pathway in the vascular remodeling process. The composition and mechanical properties of SIS were characterized. Full-thickness vaginal defects were established in 10 minipig donors, with 4 cm lengths removed and replaced by an equal sized SIS scaffolds. The neovaginas were subjected to macroscopic, histological, immunohistochemical and molecular evaluations at 4 and 12 weeks after the surgery. Four weeks after the operation, extracellular matrix reorganization and complete coverage of the surface of the luminal matrix by vaginal epithelium were observed, accompanied by the formation of a microvascular network and the regeneration of smooth muscles, albeit disorderly arranged. Twelve weeks after implantation, enhancements were seen in the formation of the multi-layered squamous epithelium, angiogenesis, and large muscle bundle formation in the vagina. Additionally, the expression levels of angiogenesis-related proteins, proliferation-related proteins and Hippo pathway-related proteins in the neovagina were significantly increased. These results indicate that SIS could be used to reconstruct large vaginal defects and that the vascular remodeling process is potentially regulated by the Hippo pathway.
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Intestino Delgado , Remodelação Vascular , Feminino , Animais , Suínos , Via de Sinalização Hippo , Porco Miniatura , Vagina/cirurgiaRESUMO
Background: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare form of autoimmune encephalitis caused by anti-NMDA receptor antibodies. This disease mainly affects women of childbearing age and is commonly associated with ovarian teratoma. However, the relationship between anti-NMDA receptor encephalitis and ovarian teratoma and the role of anti-NMDA receptor antibody in the relationship remain unclear. Objectives: This study aimed to describe 15 cases of anti-NMDA receptor encephalitis (5 with ovarian teratoma), review literature, and reinforce the gynecologist's knowledge of this disorder. Methods: Clinical data of 15 patients from January 2015 to December 2020 admitted to The Second Hospital of Hebei Medical University were collected and analyzed. The diagnosis of anti-NMDA receptor encephalitis was based on the presence of anti-NMDA receptor antibodies in cerebrospinal fluid (CSF) and/or serum. Laparoscopic teratoma removal was performed in patients with ovarian teratoma. All patients had received immunotherapy. In addition, a review of the literature was performed to reinforce the gynecologist's knowledge of this disorder. Results: A total of 15 patients with anti-NMDA receptor encephalitis were screened, of whom 5 patients were confirmed with ovarian teratoma by pathology. The most common symptoms of anti-NMDAR encephalitis with teratoma are fever (5/5, 100%), seizure (5/5, 100%), mental and behavioral disorders (4/5, 80%), and decreased consciousness (4/5, 80%). Conversely, the most common symptoms of patients without teratoma were neuropsychiatric symptoms, including headache (6/10, 60%) and mental and behavioral disorders (7/10, 70%). All patients underwent immunotherapy, including steroids, intravenous immunoglobulin (IVIG), plasma exchange, and cyclophosphamide, and 4 out of 5 patients with ovarian teratomas underwent surgical treatment. All patients had a good outcome after systemic, surgical, and immunotherapy treatment. No patient who underwent surgical treatment developed a recurrence. Conversely, 2 of 10 patients without teratoma developed an anti-NMDA receptor encephalitis recurrence. Conclusions: Patients with anti-NMDA encephalitis show severe mental and neurological symptoms. Resection of teratoma is beneficial to the relief or disappearance of symptoms and has a good prognosis. This disorder should be fully recognized by gynecologists, who play an important role in diagnosis and treatment.
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Encefalite Antirreceptor de N-Metil-D-Aspartato , Neoplasias Ovarianas , Teratoma , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/etiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Estudos Retrospectivos , Teratoma/complicações , Teratoma/diagnóstico , Teratoma/terapiaRESUMO
OBJECTIVE: To evaluate the effect of adding adipose-derived mesenchymal stem cells (ASCs) to autocross-linked hyaluronic acid (HA) gel for intrauterine adhesion (IUA) treatment. METHODS: A rat IUA model was established by mechanical curettage and infection, and then different treatments were administered to the rats on day 7 after modeling. Ninety-six rats were randomly divided into the following groups: IUA model group, gel therapy group, and combination therapy group (HA gel combined with ASCs). Eight rats per group were sacrificed on days 7, 10, 14 and 21 for the subsequent experiments. Morphological changes were determined by hematoxylin-eosin staining and Masson staining. Smad3 and leukocyte inhibitory factor (LIF) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: The endometrial lines in the gel therapy group and the combination therapy group were more complete than those in the model group. Masson staining showed that fibrosis area rates in the gel therapy group and the combination therapy group were significantly lower than those in the model group on day 7(P < 0.05). During the observation period, the fibrosis area rates in the combination therapy group remained lower than those in the model group (P < 0.05). The mRNA expression of Smad3 in the combination therapy group was lower than that in the model group and gel therapy group during the observation period (P < 0.05). The mRNA expression level of LIF in the combination therapy group was higher than that in the model group and the gel therapy group throughout the observation period (P < 0.05). CONCLUSIONS: HA gel was effective in preventing the IUA adhesion formation at the early stage of the observation period, while ASC enhanced this effect throughout the observation period. Gel and ASC composites helped to improve endometrial receptivity.
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Ácido Hialurônico/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Aderências Teciduais/terapia , Doenças Uterinas/terapia , Animais , Feminino , Fibrose , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Útero/metabolismo , Útero/patologiaRESUMO
Background: Premature ovarian insufficiency (POI) is associated with severe physical damage and psychological burden on women. Transplantation of exosomes is an encouraging regenerative medicine method, which has the potential for restoring ovarian functions on POI with high efficiency. This study aims at evaluating the therapeutic efficacy of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on ovarian dysfunction of POI and the role of Hippo pathway in this exosome-mediated treatment. Methods: POI mice models were established through intraperitoneal injection of cyclophosphamide. Subsequently, transplantation of hUCMSC-Exos was conducted to administer POI mice. Ovaries and plasma of these mice models were harvested after two weeks of treatment. Ovarian morphology and follicle number were assessed by hematoxylin and eosin staining. Moreover, ELISA was used to detect hormone levels, which are related to ovarian function in serum. To assess the recovery of reproductive ability, we recorded the rate of pregnancy, the amount of offspring, and the time of birth in different groups. To explore the underlying mechanisms of exosome-mediated treatment for ovarian function recovery, the proliferation of ovarian cells in vivo was detected by immunohistochemistry and immunofluorescence staining. Additionally, we conducted EdU and CCK-8 assays to assess the proliferative ability of ovarian granulosa cells (GCs) that were cultured in vitro. Western blot analysis was conducted to estimate the proteins levels of Hippo- and proliferation-associated molecules in vivo and in vitro. Results: After transplantation of hUCMSC-Exos, the ovarian function-related hormone levels and the number of ovarian follicles returned to nearly normal degrees. Meanwhile, there was a significant improvement in reproductive outcomes after exosomal treatment. Furthermore, the improvement of ovarian function and proliferation was associated with the regulation of Hippo pathway. In vitro, co-culture with exosomes significantly elevated the proliferation of ovarian GCs by regulating Hippo pathway. However, the positive effects on the proliferation of GCs were significantly depressed when key Hippo pathway molecule was inhibited. Conclusion: This study suggested that hUCMSC-Exos promoted ovarian functions and proliferation by regulating the Hippo pathway. Therefore, exosomal transplantation could be a promising and efficient clinical therapy for POI in the near future.
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Exossomos/transplante , Via de Sinalização Hippo/fisiologia , Células-Tronco Mesenquimais/ultraestrutura , Insuficiência Ovariana Primária/terapia , Cordão Umbilical/citologia , Animais , Proliferação de Células , Exossomos/fisiologia , Feminino , Células da Granulosa/fisiologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Ovário/crescimento & desenvolvimento , Ovário/fisiopatologia , Insuficiência Ovariana Primária/fisiopatologiaRESUMO
Premature ovarian insufficiency (POI) is a complex endocrine disease that severely affects the physiological and reproductive functions of females. The current conventional clinical treatment methods for POI are characterized by several side effects, and most do not effectively restore the physiological functions of the ovaries. Transplantation of mesenchymal stem cells (MSCs) is a promising regenerative medicine approach, which has received significant attention in the management of POI with high efficacy. Associated pre-clinical and clinical trials are also proceeding orderly. However, the therapeutic mechanisms underlying the MSCs-based treatment are complex and have not been fully elucidated. In brief, proliferation, apoptosis, immunization, autophagy, oxidative stress, and fibrosis of ovarian cells are modulated through paracrine effects after migration of MSCs to the injured ovary. This review summarizes therapeutic mechanisms of MSCs-based treatments in POI and explores their therapeutic potential in clinical practice. Therefore, this review will provide a theoretical basis for further research and clinical application of MSCs in POI.
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INTRODUCTION: The use of 3D-bioprinted ovaries has been proven to be a promising technique for preserving fertility. Stereology is an accurate method to obtain quantitative 3D information and the stereological data is the basis for 3D bioprinting ovaries. METHODS: In this study, six female mice were used to acquire the ovarian tissues. One of the two paraffin-embedded ovaries of each mouse was cut into 5 µm sections, and the other was cut into 15 µm sections and then subjected to haematoxylin and eosin staining and anti-follicle stimulating hormone receptor antibody immunohistochemistry. The volume and volume fractions of ovaries were measured by the Cavalieri method. Then, the numerical densities and total numbers of ovarian granulosa cells (OGCs) and primordial, preantral and antral follicles in serial sections were estimated using design-based stereology. RESULTS: The ovarian volume was 2.50 ± 0.32 mm3. The volume fractions of the cortex, medulla, follicles and OGCs were 86.80% ± 2.82, 13.20% ± 2.82%, 5.60% ± 0.25% and 81.19% ± 2.57%, respectively. The numerical densities of OGCs, the primordial, preantral and antral follicles were 2.11 (± 0.28) × 106/mm3, 719.57 ± 18.04/mm3, 71.84 ± 3.93/mm3 and 17.29 ± 3.54/mm3, respectively. The total number of OGCs and follicles per paraffin-embedded ovary were 5.26 (± 0.09) × 106 and 2013.66 ± 8.16. CONCLUSIONS: The study had obtained the stereological data of the mice ovaries, which contribute to a deeper understanding of the structure of the ovaries. Meanwhile, the data will supply information for 3D bioprinting ovaries.
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BACKGROUND: lncRNAs-miRNAs-mRNAs networks play an important role in Gastric adenocarcinoma (GA). Identification of these networks provide new insight into the role of these RNAs in gastric cancer. OBJECTIVES: Biological information databases were screened to characterize and examine the regulatory networks and to further investigate the potential prognostic relationship this regulation has in GA. METHODS: By mining The Cancer Genome Atlas (TCGA) database, we gathered information on GA-related lncRNAs, miRNAs, and mRNAs. We identified differentially expressed (DE) lncRNAs, miRNAs, and mRNAs using R software. The lncRNA-miRNA-mRNA interaction network was constructed and subsequent survival examination was performed. Representative genes were selected out using The Biological Networks Gene Ontology plug-in tool on Cytoscape. Additional analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were used to screen representative genes for functional enrichment. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to identify the expression of five candidate differential expressed RNAs. RESULTS: Information of samples from 375 cases of gastric cancer and 32 healthy cases (normal tissues) were downloaded from the TCGA database. A total of 1632 DE-mRNAs, 1008 DE-lncRNAs and 104 DE-miRNAs were identified and screened. Among them, 65 DE-lncRNAs, 10 DE-miRNAs, and 10 DE-mRNAs form lncRNAs-miRNAs-mRNAs regulatory network. Additionally, 10 lncRNAs and 2 mRNAs were associated with the prognosis of GA. Multivariable COX analysis revealed that AC018781.1 and VCAN-AS1 were independent risk factors for GA. GO functional enrichment analysis found DE-mRNA was significantly enriched TERM (P < 0.05). The KEGG signal regulatory network analysis found 11 significantly enrichment networks, the most prevailing was for the AGE-RAGE signaling pathway associated with Diabetic complications. Results of RT-qPCR was consistent with the in silico results. CONCLUSIONS: The results of the present study represent a view of GA from a analysis of lncRNA, miRNA and mRNA. The network of lncRNA-miRNA-mRNA interactions revealed here may potentially further experimental studies and may help biomarker development for GA.
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Adenocarcinoma/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biologia Computacional , Bases de Dados Genéticas , Epistasia Genética/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologiaRESUMO
A variety of factors can cause vaginal loss. The patients are suffering from great psychological and physical pain, and there is an urgent need for vagina reconstruction. 3D-bioprinting is expected to achieve vaginal morphological restoration and true functional reconstruction. The current study aimed to explore the biomimetic 3D vagina tissue printing with acellular vagina matrix (AVM) bioink. The AVM from pig was converted to bioink by 15% gelatin and 3% sodium alginate mixed with the AVM solution. Rheology, scanning electron microscopy and HE staining were performed to characterize the bioink's viscosity, morphologies and biocompatibility. After printing, the viability of bone marrow mesenchymal stem cells (BMSCs) in the printed 3D scaffolds in vitro was investigated by a live/dead assay kit. Then, subcutaneous transplantation in rats were divided randomly into 3D scaffold group and 3D scaffold encapsulating CM-Dil-labeled BMSCs group. The results of HE, immunohistochemistry and immunofluorescence staining revealed that 3D scaffold encapsulating BMSCs expressed significant effects on the vascularization and epithelization of the printed vagina tissue, and the BMSCs could acquire the phenotype of vaginal epithelial cells and endothelial-like cells. The work showed that the biomimetic 3D vagina tissue with AVM bioink encapsulating BMSCs is a promising approach for vagina reconstruction.
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Materiais Biomiméticos/química , Bioimpressão/métodos , Matriz Extracelular/química , Transplante de Células-Tronco Mesenquimais/métodos , Procedimentos de Cirurgia Plástica/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Vagina/cirurgia , Alginatos/química , Animais , Diferenciação Celular , Feminino , Gelatina/química , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Reologia , Suínos , Alicerces Teciduais/química , Vagina/patologiaRESUMO
BACKGROUND: This study aims to retrieve the stereological data from rat vaginas for 3D printing tissue-engineered vaginas. METHODS: In this study, five female Sprague-Dawley rats, aged 8-12 weeks, were used to obtaining the vagina tissues. Each vagina was divided into eight segments fixed in 4% paraformaldehyde and embedded in paraffin, whose two consecutive sections of each block were stained using hematoxylin and eosin (H&E) and anti-α-actin antibody with immunohistochemistry staining, respectively. The thickness of the epithelium, lamina propria, the smooth muscle layer, and the adventitia layer are measured. Then, the volume density of the epithelial cells and smooth muscle cells are counted using design-based stereology. RESULTS: The length and width of the rat vaginas were 2 and 1.5 cm, respectively. The thickness of the epithelium, lamina, propria, and adventitia layer was measured, and no significant difference was observed. However, the thickness of the smooth muscle layer was significantly different among these eight segments. The smooth muscle layer of the lower vagina is thicker than the upper vagina. The average volume density of epithelial cells and smooth muscle cells is 1.61×109/cm3 and 5.38×108/cm3. There was a significant difference observed. CONCLUSIONS: We had successfully retrieved the stereological data of the vaginas. The gained data will supply us with the information for 3D printing vaginas and new insights into the structure of the vagina.
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Diagnosis of numerous cancers has been closely linked to the expression of certain long non-coding RNAs. This study aimed to evaluate levels of plasma FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) relative to non-small-cell lung carcinoma (NSCLC) diagnosis.The level of FEZF1-AS1 in the blood plasma of 126 NSCLC patients and 62 healthy controls was examined by quantitative real-time polymerase chain reaction.Plasma FEZF1-AS1 of the NSCLC group was increased compared with that in the control group (Pâ<â.0001). Plasma FEZF1-AS1 could distinguish patients with NSCLC from healthy individuals via the area under the ROC curve (AUC) of 0.855 (95% CIâ=â0.800-0.909; Pâ=â.000). FEZF1-AS1 combined with neuron-specific enolase increased the area under the (ROC) curve to 0.932 (95% CIâ=â0.897-0.968; Pâ=â.018). A high expression level of plasma FEZF1-AS1 was associated with some clinical features of NSCLC. Increased expression of FEZF1-AS1 greatly improved the risk of NSCLC (adjusted ORâ=â2.42; 95% CIâ=â1.23-4.76). A significant concentration-dependent relationship was noted between risk of NSCLC and higher FEZF1-AS1 expression (P for trend <.001).Plasma FEZF1-AS1 could potentially be used as a biomarker for NSCLC diagnosis.