La seguridad de las placentas humanas utilizadas como materia prima farmacéutica desde el enfoque bioético / Human placenta safety used as pharmaceutical raw material based on the bioethical approach

Introducción: El uso de la placenta humana como materia prima farmacéutica se debe al contenido de sustancias biológicamente activas. El Centro de Histoterapia Placentaria -HISPLACEN- investiga, desarrolla, produce y comercializa productos de origen placentario. Objetivo: Analizar el proceso de aseguramiento y control para certificar la calidad de las placentas humanas como materia prima farmacéutica, desde el enfoque bioético en HISPLACEN. Material y Métodos: Se realizó un estudio descriptivo y analítico. Se definió como objeto de investigación: el proceso de aseguramiento y control para certificar la calidad de las placentas humanas en HISPLACEN, y su implantación en el período (2017-2021). Fueron revisados en el estudio, los documentos del Sistema de Gestión de la Calidad institucional, las regulaciones sobre Buenas Prácticas del CECMED, y la literatura científica sobre Bioética. Resultados: Las etapas del proceso de aseguramiento y control de la calidad para la certificación de las placentas se describieron y analizaron, destacándose la aplicación del enfoque bioético en su implantación. Se identificó la correspondencia de una ética humana y ambientalista de interrelación multidisciplinaria y entre los actores del ecosistema empresarial. Todo ello centrado en las dimensiones relativas a la ciencia y la tecnología para la fabricación de medicamentos. Conclusiones: Se evidenció el cumplimiento de los principios bioéticos en la certificación de las placentas humanas lo que potenció el desarrollo de un proceso tipificado por la integralidad, funcionalidad, eficacia y robustez. Este órgano biológico empleado como materia prima se abordó desde la multidimensionalidad -científica, tecnológica y bioética- del proceso descrito en sus tres etapas, lo que impacta positivamente, al focalizarse en un objetivo común: garantizar la salud y el bienestar de las personas, unido a la protección medioambiental.

Introduction: The use of human placenta as pharmaceutical raw material is due to the content of biologically active substances. The Placental Histotherapy Center (HISPLACEN) researches, develops, produces, and markets products of placental origin. Objective: to analyze the assurance and control process to certify the quality of the human placenta as a raw material in the biopharmaceutical industry, based on the bioethical approach. Material and Methods: A descriptive and analytical study was carried out. The process of quality assurance and control of the human placenta in HISPLACEN, and its implementation in the period 2017-2021 was defined as the research object. The documentation of the institutional Quality Management System, Good Practices regulations of the CECMED, and the scientific literature on Bioethics were reviewed. Results: The stages of the quality assurance and control of the placenta process and its derived products were described and analyzed, highlighting the application of the bioethical approach in its implementation. The correspondence of a human and environmental ethics of multidisciplinary interrelation and between the actors involved in the entrepreneurial ecosystem was identified. All this focused on the dimensions related to science and technology in the manufacture of medicines. Conclusions: The compliance of bioethical principles in the certification of human placentas was evidenced, which promoted the development of a process typified by comprehensiveness, functionality, efficacy, and robustness. This biological organ used as raw material was approached from multidimensionality -scientific, technological and bioethical - of the process focused on a common objective: guaranteeing human health and well-being, together with environmental protection.

Effects of human placenta tablets combined with active folic acid and compound nutrient tablets on Th1 cytokines and hormone levels in pregnant patients with threatened miscarriage / 中国基层医药

Objective:To investigate the effects of human placenta tablets combined with active folic acid and compound nutrient tablets on Th1 cytokines and hormone levels in pregnant patients with threatened miscarriage.Methods:A total of 226 pregnant patients with threatened miscarriage who received treatment in Linyi Traditional Chinese Medicine Hospital from April to September 2021 were included in this study. They were randomly divided into a control group and an observation group, with 113 patients in each group. The control group was treated with human placenta tablets. The observation group was treated with human placenta tablets combined with active folic acid and compound nutrient tablets. All patients were treated for 4 weeks. Before and after treatment, serum levels of Th1 cytokines, β-human chorionic gonadotropin, progesterone, and estradiol as well as the rate of success of protection against miscarriage, adverse reactions, and perinatal complications were compared between the two groups.Results:After 4 weeks of treatment, serum levels of interleukin-2, tumor necrosis factor-α, and interferon-γ in the observation group were significantly lower than those in the control group ( t = 27.53, 20.99, 31.69, all P < 0.001). Serum levels of β-human chorionic gonadotropin, progesterone, and estradiol in the observation group were (143.79 ± 9.56) IU/L, (36.43 ± 4.71) ng/L, (234.72 ± 13.29) pmol/L, which were significantly higher than (122.53 ± 7.47) IU/L, (29.32 ± 4.22) ) ng/L, (167.86 ± 8.93) pmol/L in the control group ( t = 18.63, 11.95, 44.39, all P < 0.001). The rate of success of protection against miscarriage in the observation group was significantly higher than that in the control group (92.9% vs. 76.1%, χ2 = 12.20, P < 0.05). There were no significant differences in the incidences of adverse reactions and perinatal compilations between the two groups (both P > 0.05). Conclusion:Human placenta tablets combined with active folic acid and compound nutrient tablets can improve serum levels of Th1 cytokines and hormones, and increase the rate of success of protection against miscarriage, without increasing the incidences of adverse reactions and perinatal complications.

Modelo integral de entrenamiento microquirúrgico y neuroendovascular con placenta humana / Comprehensive microsurgical and neuroendovascular training model with human placenta

Introducción: La neurocirugía vascular, tanto la microquirúrgica como endovascular, ha progresado significativamente en el tratamiento de la patología cerebrovascular. Sin embargo, en una considerable proporción de casos este tipo de patología no puede ser resuelta definitivamente mediante un único abordaje. Por lo cual consideramos que el neurocirujano en formación debe capacitarse con ambas técnicas.Se describe un modelo de entrenamiento en microcirugía y en nociones básicas del material y técnica neuroendovascular, utilizando placenta humana y recursos de baja complejidad. Material y método: Se utilizaron 20 placentas humanas, instrumental y sutura de uso habitual en microcirugía, microscopio quirúrgico Newton®XX1, material para procedimientos endovasculares; equipo de radioscopia (arco en C Phillips BV Pulsera®), un cráneo óseo y un cabezal de fijación tipo Sugita® adaptado a su uso en laboratorio. Los ejercicios consistieron en: 1. Disección y exposición de los vasos arteriales y venosos del corion; 2. Anastomosis término-terminal, termino-lateral y latero-lateral; 3. Generación de aneurismas laterales, de bifurcación o trifurcación; 4. Creación de bypass extra-intracraneano; 5. Clipado de los aneurismas en superficie y dentro del cráneo; 6. Control angiográfico pre y post clipado. 7. Embolización con coils de los aneurismas experimentales y de vasos placentarios con partículas de Spongostan®. Resultados: Aunque los vasos tienen una estructura y consistencia diferentes a los habituales para el neurocirujano, la placenta ofrece una variabilidad de calibres y formatos donde practicar los diferentes ejercicios. Conclusión: El entrenamiento en técnicas microquirúrgicas y neurointervencionistas puede ser realizado en modelos placentarios de simulación, que permiten el desarrollo háptico progresivo previo a la realización de un procedimiento in vivo.

Objective: Describe a training model in microsurgery and neuroendovascular surgery, using human placenta and low complexity resources. Material and methods: 20 human placentas, instruments and sutures were used in microsurgery, Newton XX1 surgical microscope, material for endovascular procedures; radioscopy equipment (C-arch Phillips BV Pulsera), a bony skull and a Sugita head adapted for laboratory use. The exercises consisted of: 1. Dissection and exposure of the arterial and venous vessels of the chorion; 2. End-to-end, end-to-side, side-to-side anastomosis; 3. Generation of lateral, bifurcation or trifurcation aneurysms; 4. Creation of extra-intracranial bypass; 5. Clipping of aneurysms on the surface and inside the skull; 6. Pre and post clipping angiographic control. 7. Coil embolization of experimental aneurysms and placental vessels embolization with spongostan particles. Results: Although the vessels have a different structure and consistency than usual for the neurosurgeon, the placenta offers a variability of sizes and formats to practice the different exercises. Conclusion: Training in microsurgical and neurointerventionist techniques can be carried out in placental models, which allow progressive haptic development prior to performing an in vivo procedure.

Human placental laminin: Role in neuronal differentiation, cell adhesion and proliferation

Human placental extract has wound healing potential. Immuno-blots revealed presence of laminin in placentalextract (70 ± 0.257 lg/ml; n=3). It was purified using immuno-affinity chromatography. SDS-PAGE and SEHPLC indicated a188 kDa protein with some small peptides. Since placental laminin existed in its truncatedform, its roles in cellular migration, differentiation and wound healing were verified. Induction of cellularmigration and motility in rat fibroblasts were enhanced by placental laminin as observed from scratch woundassay. Promotion of neuronal differentiation of PC12 cells by placental laminin was observed by phase contrastmicroscopy. Confocal images showed presence of laminin on the cell surface and along the axonal processes.Significant interaction between integrin receptors and laminin responsible for cellular differentiation wasdemonstrated from co-localization experiments. Union between integrin receptor and its synthetic antagonistrevealed retarded pattern of neurite outgrowth in laminin treated cells. Animal model studies revealed fasterwound healing in the presence of placental laminin. Induction of re-epithelialization and angiogenesis inwound area by cellular proliferation and adhesion were observed. The cytokine levels showed an initial riseand gradual fall over the duration of wound healing on application of the fragmented laminin. Thus, roles ofplacental laminin in neuronal differentiation and wound healing were indicated.

Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells (HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. The secretion of pro-inflammatory cytokines (human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay (ELISA). The expression of pro-angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Relevant molecules of the nuclear factor-κB (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs (HPMSCs/ leptin) exhibited better cell proliferation, migration, and angiogenic potential (expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines (human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-κB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.

Human placenta mesenchymal stem cells-derived extracellular vesicles regulate collagen deposition in intestinal mucosa of mice with colitis / 中国组织工程研究

BACKGROUND:Intestinal fibrosis is a common complication in inflammatory bowel disease and leads to functional damage and intestinal obstruction. Intestinal fibrosis is mainly related to the imbalance of deposition and degradation of extracellular matrix components, such as collagens and fibronectins. Studies have found that mesenchymal stem cells secreted soluble bioactive substance such as extracellular vesicles via paracrine action, which exerted marked anti-fibrosis effect. OBJECTIVE: To investigate the effect of human placenta mesenchymal stem cells-derived extracellular vesicles on collagen deposition in mice with colitis. METHODS: Totally 24 BALB/c mice were randomly divided into sham operation group, model group and extracellular vesicles group, with 8 mice in each group. Except the sham operation group, the remaining mice of model group and extracellular vesicles group were treated with trinitro-benzene-sulfonic acid to induce intestinal fibrosis, once a day for 6 weeks. The mice in the extracellular vesicles group and model group were administered with extracellular vesicles and phosphate-buffered saline, respectively, at 3 weeks, once a day for 6 weeks. The therapeutic effect of extracellular vesicles was evaluated by disease active index score and the colon weight/length ratio at 1-7 weeks. Diseased intestinal segment was subjected to histological staining. Western blot assay and RT-PCR were used to measure fibrosis related indicators so as to evaluate the degree of intestinal fibrosis. RESULTS AND CONCLUSION: (1) Compared with the model group, disease active index score and the colon weight/length ratio were significantly reduced, and colonic pathology was significantly improved in the extracellular vesicles group. (2) Compared with the model group, collagen deposition in colon mucosa of mice was significantly reduced, and the expression of collagen I, collagen III and transforming growth factor-β1 decreased significantly in the extracellular vesicles group. (3) Compared with the model group, expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in mouse colon tissue were significantly increased, while the expression level of tissue inhibitor of metalloproteinase 1 was decreased in the extracellular vesicles group. (4) Results suggest that human placenta mesenchymal stem cells-derived extracellular vesicles can obviously improve the severity of colon injury and reduce the collagen deposition of intestinal mucosa in mice with enteritis.

Effects of leptin-modified human placenta-derived mesenchymal stem cells on angiogenic potential and peripheral inflammation of human umbilical vein endothelial cells (HUVECs) after X-ray radiation / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was transfected into human placenta-derived mesenchymal stem cells (HPMSCs) with lentiviral vectors. HUVECs were irradiated by X-ray at a single dose of 20 Gy. Transwell migration assay was performed to assess the migration of irradiated HUVECs. Based on the Transwell systems, co-culture systems of HPMSCs and irradiated HUVECs were established. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. The secretion of pro-inflammatory cytokines (human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-1α, IL-6, and IL-8) was detected by enzyme-linked immunosorbent assay (ELISA). The expression of pro-angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)) mRNA was detected by real-time quantitative polymerase chain reaction (RT-qPCR) assay. Relevant molecules of the nuclear factor-KB (NF-kB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were detected by western blot assay. Results showed that leptin-modified HPMSCs (HPMSCs/leptin) exhibited better cell proliferation, migration, and angiogenic potential (expressed more VEGF and bFGF). In both the single HPMSCs/leptin and the co-culture systems of HPMSCs/leptin and irradiated HUVECs, the increased secretion of pro-inflammatory cytokines (human GM-CSF, IL-1α, and IL-6) was associated with the interaction of the NF-KB and JAK/STAT signaling pathways. We conclude that HPMSCs/leptin could promote angiogenic potential and peripheral inflammation of HUVECs after X-ray radiation.

Transplacental Transfer of Glyburide in the ex vivo Human Placenta Perfusion Model / 中国药学杂志

OBJECTIVEP: To determine the ex vivo human placental transfer of glyburide from maternal circulation to the fetal circulation in Chinese Hans population. METHODS: Perfusion studies were performed on thirty-six placentas from healthy term pregnancies. The circulation of mother-placenta-fetus was set up ex vivo within minutes and accessed by studying spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments. RESULTS: Following 3 h of perfusion, the fetal transfer rate of glyburide was (1.64±0.85)%. The clearance index of glyburide was (0.05±0.03). CONCLUSION: These data suggest that tiny amount of glyburide can cross the human placenta. Glyburide could be used as a clinically effective alternative to insulin therapy.

Induction of tanshinone ⅡA on differentiation of human placenta-derived mesenchymal stem cells into cardiomyocytes and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the induction of tanshinoneⅡA (TanⅡA) on the differentiation of human placenta-derived mesenchymal stem cells (hPDMSCs) into cardiomyocytes, and to provide an experimental basis for TanⅡA as a cardiomyocyte differentiation inducer.Methods:The hPDMSCs were treated with different concentrations of TanⅡA (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 2.0, 4.0, 6.0, 8.0, and 10.0mg·L-1) , and the nontoxic dose of TanⅡA (0.1mg·L-1) was screened by MTT assay for experiment.The hPDMSCs were divided into control group, 5-aza induction (10μmol·L-1) group, and TanⅡA induction (0.1mg·L-1) group.After culture for 20d, the expressions ofα-sarcomeric actin (α-SCA) in the cells in various groups were detected with immunohistochemistry;the positive expression rates of cardiac troponin I (cTnI) in the cells in various groups were detected with immunofluorescence, and the differentation rates of cardiomyocytes were calculated.The expression levels of GATA-binding protein 4 (GATA4) , atrial natriuretic factor (ANF) , cTnI, glycogen synthase kinase-3β (GSK-3β) andβ-catenin in the cells were detected with Western blotting method.Results:The biological characteristics of hPDMSCs accorded with the mesenchymal stem cells.The MTT results showed that when the concentration of TanⅡA was more than 0.1mg·L-1, the cell survival rates were decreased with the increase of concentration;the cells in control group showed a rapid growth trend before 12d, and the proliferation activities of the cells began to decrease on the 12th day.Compared with control group, the cell activities in 5-aza induction group and TanⅡA induction group were significantly decreased (P＜0.05) .The immunohistochemistry staining results showed that the cells in control group didn't expressα-SCA, and the cells in 5-aza induction group and TanⅡA induction group expressedα-SCA, especially in TanⅡA induction group.Compared with control group, the expression levels of GATA4 (t5-aza=2.937, P5-aza＜0.05;tTanⅡA=4.769, PTanⅡA＜0.05) , ANF (t5-aza=3.728, P5-aza＜0.05;tTanⅡA=5.912, PTanⅡA＜0.05) , cTnI (t5-aza=3.623, P5-aza＜0.05;tTanⅡA=7.153, PTanⅡA＜0.05) and GSK-3β (t5-aza=2.995, P5-aza＜0.05;tTanⅡA=5.420, PTanⅡA＜0.05) proteins in the cells in 5-aza induction group and TanⅡA induction group were significantly increased, and the expression levels ofβ-catenin (t5-aza=2.985, P5-aza＜0.05;tTanⅡA=6.951, PTanⅡA＜0.05) protein were significantly decreased;compared with 5-aza induction group, the expression levels of GATA4, ANF, and GSK-3βproteins in TanⅡA induction group were increased (P＜0.05) .Conclusion:TanⅡA can induce the differentiation of hPDMSCs into cardiomyocytes, which has better effect than 5-aza, and its mechanism may be related to inhibiting the Wnt/β-catenin signaling pathway.

Induction of tanshinone 11 a on differentiation of human placenta-derived mesenchymal stem cells into cardiomyocytes and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the induction of tanshinone [1 A (Tan fl A) on the differentiation of human placenta-derived mesenchymal stem cells (hPDMSCs) into cardiomyocytes, and to provide an experimental basis for Tan IT A as a cardiomyocytc differentiation inducer. McthodS; The hPDMSCs were treated with different concentrations of Tan Fl A (0.1.0.2.0.4.0.6.0.8.1.0. 2.0. 4.0. 6.0. 8.0. and 10. 0 mg • L ). and the nontoxic dose of Tan II A <0. 1 mg • L ) was scrccncd by MTT assay for experiment. The hPDMSCs were divided into control group. 5-aza induction (10 pmol • L ) group, and Tan Fl A induction (0. 1 mg • L ) group. After culture for 20 d. the expressions of o-sarcomeric acun (o-SCA) in the cells in various groups were detected with lmmunohistochcmastry; the positive expression rates of cardiac troponin 1 (cTnl) in the cells in various groups were detected with immunofluorescence, and the differentation rates of cardiomyocytes were calculated. The expression levels of GATA-binding protein 4 (GATA4). atnal natriuretic factor (ANF). cTnl. glycogen synthase kmase-30 (GSK-30 ) and 0-catemn in the cells were detected with Western blotting method. Results: The biological characteristics of hPDMSCs accorded with the mesenchymal stem cells. The MTT results showed that when the concentration of TanFl A was more than 0. 1 mg • L . the cell survival rates were decreased with the increase of concentrations the cells in control group showed a rapid growth trend before 12 d. and the proliferation activities of the cells began to decrease on the 12th day. Compared with control group, the cell activities in 5-aza induction group and TanFl A induction group were significantly decreased < P<0. 05). The immunohistochcmistry staining results showed that the cells in control group didn' t express a-SCA. and the cells in 5-aza induction group and TanFl A induction group expressed o-SCA. cspcaally in Tan Fl A induction group. Compared with control group, the expression levels of GAT A4 ( i - 2.937. P <0.05,4.769, P ,| , <0. 05) . ANF ( t -3.728. P <0.05 j r.-5.912, P ., ,<0.05). cTnl

Lección MOODLE de anatomía e histología de la placenta humana / MOODLE lesson of the anatomy and histology of the human placenta

RESUMEN: La falta de muestras biológicas humanas existentes, debido principalmente a las limitaciones ético-morales relacionadas con su obtención, ponen en relieve la necesidad de buscar otras alternativas de enseñanza y aprendizaje de las ciencias morfológicas. En este sentido, la implementación de lecciones a través de la plataforma MOODLE proporciona la oportunidad al estudiante de interactuar en un entorno que simula una situación de aprendizaje propio del laboratorio tradicional. El objetivo del presente trabajo fue generar una lección MOODLE sobre la anatomía e histología placentaria humana, como complemento a la clase teórica presencial, para estudiantes de la carrera de Obstetricia y Puericultura. Para tal cometido, se realizó búsqueda de información, imágenes y recursos TIC en bibliotecas e internet. Paralelamente, se llevó a cabo un proceso de captura fotográfica de muestras histológicas de placenta, así como también la grabación de un alumbramiento. Posteriormente, se procedió a la articulación y montaje de las actividades en la plataforma MOODLE con un enfoque constructivista. Además, se elaboró una encuesta de satisfacción, la cual fue validada por 3 expertos. La muestra estuvo constituida por 137 estudiantes de la carrera de Obstetricia. Se confeccionó un laboratorio virtual MOODLE de anatomía e histología de la placenta humana, el cual esta constituido por múltiples actividades con orientación clínica, las cuales permiten autoevaluarse. El laboratorio virtual nos ha ayudado ha subsanar la carencia de muestras humanas y los resultados de la encuesta de satisfacción aplicada a los estudiantes señalan una valoración positiva de la iniciativa.

SUMMARY: The lack of existing human biological samples, mainly due to the ethical-moral restrictions related to obtaining these, highlights the need to search for other teaching and learning alternatives in morphological science. In this sense, the implementation of lessons by means of the MOODLE platform provides the students with the opportunity to interact in a setting that simulates a learning situation that belongs to traditional laboratories. The purpose of this work was to generate a MOODLE lesson on the anatomy and histology of the human placenta, as a complement of the traditional theoretical classroom for students of Obstetrics. To that end, TIC information, images, and resources were sought in libraries and in the Internet, and at the same time a set of histological photographs of placenta samples was made, as well as a video recording of a placental delivery. Later, the coordination and set up of activities was made in the MOODLE platform with a constructivist approach. Furthermore, a satisfaction survey was prepared which was validated by three experts. The total sample consisted of 137 students in the 2th year of obstetrics. A virtual MOODLE laboratory of the anatomy and histology of the human placenta was made, which is constituted by multiple activities with a clinical orientation that allow self-evaluation. The virtual laboratory has helped overcome the lack of human samples, and results of the satisfaction survey applied to the students indicate a positive evaluation of this initiative.

Effect of modified formula Compound Biejia Ruangan Pills on hepatic fibrosis in rats induced by CCl4 and its mechanism / 中草药

Objective: To explore the possible effects and mechanism of modified Compound Biejia Ruangan Pills (MF-CBRP) on liver fibrosis induced by CCl4 in rats. Methods: SD rats were randomly divided into control group, model group, positive control (colchicine, 0.1 mg/kg) group, CBRP group (0.594 7 g/kg), MF-CBRP high-and low-dose (1.061 0 and 0.530 5 g/kg) groups. The rat model with liver fibrosis was established by sc injection CCl4 solution (dissolved in soybean oil), twice a week for six weeks except control group. The rats in the treatment groups were administered six weeks after the model establishment. At the end of the administration, the contents of serum biochemical, hydroxyproline (Hyp), lipid peroxidation, fibrosis factor, platelet-derived factor-α (PDGF-α), and connective tissue growth factor (CTGF) were measured and the pathological changes of liver tissue were examined by HE and Masson. The level of α-SMA and the expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by immunohistochemistry and RT-PCR. Results: The results showed that MF-CBRP improved the liver function significantly through reducing the level of ALT, AST, T-Bil, ALP, Hyp, HA, LN, PC-III, IV-C, and MDA (P < 0.05, 0.01), and increasing the content of S/L, TP, ALB, SOD, and GSH (P < 0.05, 0.01). MF-CBRP also reduced the expression of PDGF-α, CTGF, α-SMA, MMP-2, and TIMP-1 mRNA (P < 0.01) and improved the pathological changes of liver histopathology. Compared with CBRP, MF-CBRP anti-hepatic fibrosis effect was slightly weakened. Conclusion: The results suggested that MF-CBRP may against hepatic fibrosis by reducing oxidative stress, inhibiting collagen fibrillation, reversing hepatic stellate cell activation, and inhibiting the expression of hepatic growth factor. However its anti-fibrosis activity and mechanism was weaker than the original CBRP in a certain extent.

Effect of human placenta on ovarian function and endometrial receptivity in patients with ovarian dysfunction / 中国综合临床

Objective To investigate the effect of human placenta on ovarian function and endometrial receptivity in patients with ovarian dysfunction. Methods From January 2017 and August 2017, one hundred and twenty patients of ovarian hypofunction infertility who received therapy in Liuzhou Worker′s Hospital were selected and were randomly divided into observation group ( 60 cases) and control group ( 60 cases) ,the control group was treated with oral letrozole at the 2nd to 5th day of the menstrual cycle for 5 consecutive days,at the same time, vitamin E soft capsule was taken orally until the next menstrual cycle, the letrozole usage in the observation group was the same as that in the control group,and human placenta tablets were taken orally until the next menstrual cycle. Both groups were treated for 3 menstrual cycles continuously. The changes of luteinizing hormone (LH),follicle stimulating hormone (FSH),estradiol (E2),resistance index (RI),pulsation index (PI),endometrial thickness and shape during and after ovulation were compared between the two groups before and after treatment. The efficacy of ovulation induction,ovulation rate and pregnancy rate were compared. Results After treatment,two groups of FSH,E2 treatment were decreased significantly ( P<0. 05) ,the FSH,E2,in the observation group were significantly lower than those of the control group ((9. 62±1. 04)U/L vs. (12. 45±1. 13)U/L,(174.85±36.21)pmol/L vs. (188.69±27.92)pmol/L)(t=14.274,2.345,P<0.05),there were no obvious changes in LH in the observation group and the control group( P>0. 05);after treatment,the endometrial thickness in the observation group was significantly higher than that of the control group ((12. 25±0. 13)mm vs. (10. 97±0. 10)mm)(t=60. 452,P<0. 05); after treatment,the RI and PI of the two groups were significantly lower than those before treatment (P<0. 05),the RI,PI in the observation group were significantly lower than those of the control group ((0.54±0.03)vs. (0.59±0.03),(1.23±0.06)vs. (1.43±0.08))(t=9.129, 15. 492,P<0. 05);the total effective rate of ovulation induction in the observation group was significantly higher than that in the control group (93. 33％(56/60)vs. 75. 00％(45/60))(χ2=7. 566,P<0. 05); there was no significant difference in ovulation rate between the two groups ( P>0. 05) ,but the pregnancy rate in observation group was obviously higher than that of the control group ( 31. 67％ ( 19/60) vs. 15. 00 ( 9/60) ) (χ2=4. 658, P<0. 05 ) . Conclusion In patients with ovarian dysfunction in the application of human placenta effect is significant,which can effectively improve the ovarian function and endometrial receptivity, improve pregnancy rate,clinical application value is high.

Comparison of mesenchymal stem cells from human placenta and umbilical cords / 军事医学

Objective To compare two sources of mesenchymal stem cells ( MSCs) from human placenta and umbilical cord, and to optimize a technical solution for bench or clinical studies of MSCs.Methods MSCs were isolated from human placenta and umbilical cord and expanded for analysis.The cell morphology was observed under invert microscope, the immunophenotypic feature of MSCs was analyzed with flow cytometer, the cell proliferation ability was determined by cell cycle assay and cell doubling time, the cell differentiation potential was evaluated by osteogenic and adipogenic induction in vitro as well.Results Both sources of MSCs were adherent cells and exhibited fusiform and fibrous morphology. Furthermore, both MSCs high expressed CD90 and CD105, and were negative for the markers of CD34, CD45 and HLA-DR.The population doubling time of MSCs form human placenta and umbilical cord was 39.5 h and 40.8 h separately, and the results of cell cycle analysis showed that the percent of the two sources of MSCs in G0/G1 phase was 52.12%and 57.50% respectively. The above results demonstrated that both sources of MSCs possessed the similar biological characteristics in morphology, phenotype and as well as proliferation ability.In addition, both of them could be induced into osteoblasts and adipocytes in vitro.Conclusion MSCs from human placenta have the similar biological characteristics to these from human umbilical cord, and both of them are better candidates for bench and clinical research.

Validación del sistema ultramicroelisa en la certificación de placenta humana como materia prima farmacéutica y cosmética / Validation of the Ultra Micro Elisa for certification of human placent as a source of pharmaceuticals and cosmetics

INTRODUCCIÓN: el Laboratorio de Control Viral de la Planta Derivados de la Placenta realiza la certificación de la placenta humana como materia prima farmacéutica y cosmética mediante el sistema ultramicroanalítico. OBJETIVO: validar el sistema ultramicroelisa de determinación de antígeno de superficie del virus de la hepatitis B, anticuerpos contra el virus de la hepatitis C y virus de inmunodeficiencia humana tipo 1 y 2 en muestras de suero de cordón umbilical. MÉTODOS: se realizó la calificación de la operación y la validación del desempeño analítico de los sistemas UMELISA HBsAg Plus, UMELISA HCV y UMELISA HIV 1+2 Recombinant empleandocomo sistemas de referencia el Hepanostika HBsAg Uni-FormII, Hepanostika HCV Ultra y Vironostika HIV-Uni-Form II Ag/Ab. RESULTADOS: la calificación de la operación para las tres técnicas analíticas resultó satisfactoria. Los parámetros de especificidad diagnóstica y analítica fueron de 100 %, así como la concordancia con las técnicas de referencia. El coeficiente de variación fue menor del 10 % durante el estudio de precisión interensayo, menor que el 20 % intraensayo y se demostró la robustez de las técnicas para pequeños cambios en la temperatura de incubación. CONCLUSIONES: los sistemas ultramicroelisa utilizados como método de control de la calidad de la placenta humana resultaron específicos, precisos y robustos en las condiciones ensayadas, por lo que pueden emplearse de manera segura y confiable.

INTRODUCTION: the Viral Control Laboratory of the Placenta Derivatives Production Plant certifies the human placenta as pharmaceutical and cosmetic raw material by means of the microultra analytic system. OBJECTIVE: to validate the Ultra Micro System for determination of hepatitis B surface antigen, antibodies to Hepatitis C Virus, and Immunodeficiency Human Virus Type 1 and 2 in umbilical cord serum samples. METHODS: the qualification of the operation and the validation of the analytic performance of the UMELISA HBsAg Plus system, UMELISA HCV and UMELISA HIV 1+2 Recombinant using the Hepanostika HBsAg Unite-Form II, Hepanostika Ultra HCV and Vironostika HIV-unite-Form II Ag/Ab as reference systems. RESULTS: the qualification of the operation for the three analytic techniques was satisfactory. The diagnostic and analytic specificities were 100 %; as well as the agreement with the reference techniques. The variation coefficient was lower than 10 % during the inter-assay precision study, below 20 % intra-assay and the robustness of the techniques was shown to manage small changes in the incubation temperature. CONCLUSIONS: the ELISA Ultra Micro Systems used as quality control methods of the human placenta were specific, precise and robust under the tested conditions, so they can be safely and reliably used.

Regulatory effects of IFN-γon the expression of PDL2 on human placenta mesenchymal stem cells (hPMSCs) and the hPMSCs-induced differentiation of peripheral blood CD8+IL-10+T cell subsets / 中华微生物学和免疫学杂志

Objective To investigate the regulatory effects of IFN-γon the expression of pro-grammed death ligand 2 (PDL2) on human placenta mesenchymal stem cells (hPMSCs) and the hPMSCs-induced differentiation of peripheral blood CD 8+IL-10+T cell subsets .Methods hPMSCs were isolated from mature human placenta by enzyme digestion .The expression of PDL2 on hPMSCs and the regulatory effects of IFN-γon PDL2 expression were detected by RT-PCR and flow cytometry ( FCM ) , respectively . Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects by density gradient centrif-ugation.T cells were purified with sheep red blood cells .FCM was used to detect the ratios of CD 8+IL-10+T cell subsets in PHA or CD3/CD28 beads activated T cells in the presence of hPMSCs treated with Anti-PDL2 McAb or IFN-γ.Results PDL2 molecules were highly expressed on hPMSCs that could be further enhanced by IFN-γ.The results of FCM demonstrated that hPMSCs could induce the differentiation of CD 8+IL-10+T cell subsets .The ratios of CD8+IL-10+T cell population in T cells activated by different stimulators including PHA and CD3/CD28 beads were significantly increased in the presence of hPMSCs as compared with those without hPMSCs (P<0.01).In addition, the antibody blocking experiments indicated that PDL 2 McAb down-regulated the percentages of CD 8+IL-10+T cell subsets in PHA or CD 3/CD28 beads stimulated T cells in the presence of hPMSCs as compared with those of unblocked groups .CD8+IL-10+T cell subsets were up-regulated in IFN-γtreated hPMSCs groups as compared with those of untreated groups .Conclusion hPMSCs could induce the differentiation of peripheral blood T cells into CD 8+IL-10+T cell subsets , which was enhanced by PDL 2 expressed on hPMSCs .IFN-γcould promote the differentiation of CD 8+IL-10+T cell subsets induced by hPMSCs through up-regulating the expression of PDL2 on hPMSCs.

Study of optimal matching conditions for hemoglobin polymerization process / 国际生物医学工程杂志

Objective To study the optimization process of matching conditions using glutaraldehyde (GDA) as crosslinking agent of hemoglobin based oxygen carriers (HBOCs),to further reduce the average molecular weight and the content of super-weight molecular,and improve the conversion ratio of polymerization.Methods The orthogonal designs were done on the basis of the previous single influencing factor research of human placenta hemoglobin crosslinking GDA.Three factors were selected including molar ratio of GDA to hemoglobin,mass concentration of hemoglobin and the rate of the feeding GDA.Results The molar ratio of GDA to hemoglobin is the most important influencing factor on the molecular weight distribution of polymerized hemoglobin,followed by the mass concentration of hemoglobin and the rate of feeding GDA.When analyzing the impact on the mean molecular weight,there were significant differences between mean molecular weight corresponding to different molar ratios of GDA to hemoglobin (P＜0.05),while there was no statistical significance between mean molecular weight corresponding to different mass concentrations of hemoglobin and the rates of feeding GDA (P＞0.05).When analyzing the impact on the effective conversion ratio,there were significant differences between effective conversion ratios corresponding to different molar ratios of GDA to hemoglobin and different mass concentrations of hemoglobin (P＜0.05),while there were no statistical significances between effective conversion ratios corresponding to different rates of feeding GDA (P＞0.05).When analyzing the impact on the content of super-weight molecular,there were significant differences between content of super-weight molecular corresponding to different molar ratios of GDA to hemoglobin,while there were no statistical significances between content of super-weight molecular corresponding to different mass concentrations of hemoglobin and different rates of feeding GDA.Conclusions The optimal matching conditions of hemoglobin polymerization process were determined by orthogonal designs.

The role of placental indoleamine 2,3-dioxygenase in human pregnancy

Munn et al. made a scientific observation of major biological importance. For the first time they showed that in the mammal the fetus does survive an immune attack mounted by the mother, and that the mechanism responsible for the survival depends on the fetus and placenta 'actively' defending itself from attack by maternal T cells by means of an enzyme indoleamine 2,3-dioxygenase (EC 1.13.11.42) dependent localised depletion of L-tryptophan. These findings raise critical questions for disease and its prevention during human pregnancy. Specifically, the role of this mechanism (discovered in mouse) in the human, and the extent to which defective activation of this process is responsible for major clinical diseases are unknown. Therefore some key facts about this enzyme expressed in the human placenta have been studied in order to test whether Munn et al.'s findings in mouse are met for human pregnancy. This short review attempts to describe our experimental work on human placental indoleamine 2,3-dioxygenase.

Advances in human placenta-derived stem cells for liver regeneration / 中华肝胆外科杂志

Human placenta-derived stem cells (hPD-SCs) are a mixed group of stem cells.Stem cell medicine has applications for organ damage or failure through regenerative,anti-apoptotic,anti-inflammatory and anti-tumor properties in addition to cell function recovery.Presently,human placenta mesenchymal stem cells (hPMSCs) have similar characteristics to the differentiation of hepatocyte-like cells by promoting hepatocyte regeneration,anti-hepatocyte apoptosis and anti-liver fibrosis,in vitro or in animal models.To further our investigation,a summary of the origin,sorting and biological properties of hPDSCs along with a narration of hPDSCs for liver disease therapy was written.This leads to a discussion for new ideas to further explore cell treatment for liver disease.

TonEBP and SMIT expression in human placenta / 대한해부학회지

Tonicity-responsive enhancer binding protein (TonEBP) is a signal transcription factor of transporters such as sodium-myo-inositol cotransporter (SMIT), aldose reductase. TonEBP has a variety of functions such as control of intracellular osmolytes and immunomodulating. It is known that TonEBP is abundant in the placenta, but location and function aren't known. The aim of this study is to describe the localization of TonEBP in the placenta. We assayed the immunohistochemistry of TonEBP and performed in situ hybridization of SMIT in normal human full term placenta. In normal human full term placenta, TonEBP was in villous trophoblasts, extravillous trophoblasts and some endothelial cells. The result of the in situ hybridization of SMIT was similar to that of immunohistochemistry of TonEBP. Neither TonEBP nor SMIT was present in TonEBP knockout mouse placenta. This shows TonEBP is a key factor in SMIT transcription. TonEBP may play an important role in transporting of inositol to fetus in placenta.