OBJECTIVE: To explore the association between postpartum depression (PPD) and transforming growth factor-β (TGF-β) concentrations in human colostrum. METHODS: Participants were recruited from a maternal and infant cohort established in a tertiary general hospital in Guangdong Province between December, 2020 and September, 2021. In the afternoon of the second postpartum day, the women were evaluated with Edinburgh Postnatal Depression Scale (EPDS) for screening PPD (defined as a score of 10 or higher). The women with PPD were matched at a 1:1 ratio with women without PPD with maternal age difference within 5 years and the same mode of delivery. Colostrum samples were collected in morning on the third postpartum day for measurement of TGF-β concentrations using enzyme-linked immunosorbent assay (ELISA), and the association between EPDS scores and TGF-β concentrations was analyzed in the two groups. RESULTS: A total of 90 women were included in the final analysis. The mean concentrations of TGF-β1, TGF-β2 and TGF-β3 in the colostrum were 684.03 (321.22-859.25) pg/mL, 5116.50±1747.04 pg/mL and 147.84±48.68 pg/mL in women with PPD, respectively, as compared with 745.67 (596.00-964.22) pg/mL, 4912.40±1516.80 pg/mL, and 168.21±48.15 pg/mL in women without PPD, respectively. Compared with women without PPD, the women with PPD had significantly lower concentrations of TGF-β1 (P=0.026) and TGF-β3 (P=0.049) in the colostrum. Spearman correlation analysis revealed that the EPDS scores were negatively associated with the concentrations of TGF-β1 (r=-0.23, P=0.03) and TGF-β3 (r=-0.25, P=0.02) in the colostrum. CONCLUSION PPD is associated with decreased concentrations of TGF-β1 and TGF-β3 in human colostrum, suggesting the need of early PPD screening and interventions during pregnancy and the perinatal period to minimize the impact of PPD on human milk compositions.
Child, Preschool ; Cohort Studies ; Colostrum ; Depression, Postpartum/diagnosis* ; Female ; Humans ; Infant ; Postpartum Period ; Pregnancy ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factor beta3 ; Transforming Growth Factors

Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and arranged to harvest EMPs in two parts: the first part consisted of EMP and EMP and the second part included EMP, EMP, and EMP. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student's t-test was used when two groups were compared. Results: Compared with EMP- and EMP-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40, P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52, P < 0.01), the number of tube formations was markedly reduced by 70% in the EMP group (P < 0.001) in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMP was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed that TGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression of TGFβ2 in HUVECs was inhibited by treatment with EMP and EMP. Conclusions MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.
Cell Hypoxia ; genetics ; physiology ; Cell Movement ; genetics ; physiology ; Endothelial Cells ; metabolism ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; MicroRNAs ; genetics ; metabolism ; Neovascularization, Physiologic ; genetics ; physiology ; Transforming Growth Factor beta2 ; genetics ; metabolism

Bone formation is important for the reconstruction of bone-related structures in areas that have been damaged by inflammation. Inflammatory conditions such as those that occur in patients with rheumatoid arthritis, cystic fibrosis, and periodontitis have been shown to inhibit osteoblastic differentiation. This study focussed on dental follicle stem cells (DFSCs), which are found in developing tooth germ and participate in the reconstruction of alveolar bone and periodontal tissue in periodontal disease. After bacterial infection of inflamed dental tissue, the destruction of bone was observed. Currently, little is known about the relationship between the inflammatory environment and bone formation. Osteogenic differentiation of inflamed DFSCs resulted in decreased alkaline phosphatase (ALP) activity and alizarin red S staining compared to normal DFSCs. Additionally, in vivo transplantation of inflamed and normal DFSCs demonstrated severe impairment of osteogenesis by inflamed DFSCs. Protein profile analysis via liquid chromatography coupled with tandem mass spectrometry was performed to analyse the differences in protein expression in inflamed and normal tissue. Comparison of inflamed and normal DFSCs showed significant changes in the level of expression of transforming growth factor (TGF)-β2. Porphyromonas gingivalis (P.g.)-derived lipopolysaccharide (LPS) was used to create in vitro inflammatory conditions similar to periodontitis. The osteogenic differentiation of LPS-treated DFSCs was suppressed, and the cells displayed low levels of TGF-β1 and high levels of TGF-β2. DFSCs treated with TGF-β2 inhibitors showed significant increases in alizarin red S staining and ALP activity. TGF-β1 expression was also increased after inhibition of TGF-β2. By examining inflamed DFSCs and LPS-triggered DFSCs, these studies showed both clinically and experimentally that the increase in TGF-β2 levels that occurs under inflammatory conditions inhibits bone formation.
Adolescent ; Alkaline Phosphatase ; metabolism ; Animals ; Cell Differentiation ; Cell Proliferation ; Cell Survival ; Cells, Cultured ; Dental Sac ; cytology ; metabolism ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunohistochemistry ; Male ; Mass Spectrometry ; Mice ; Nitric Oxide ; metabolism ; Osteogenesis ; drug effects ; Polymerase Chain Reaction ; Staining and Labeling ; Stem Cells ; cytology ; metabolism ; Transforming Growth Factor beta2 ; pharmacology ; Young Adult

OBJECTIVETo explore the effect of curcumin on TGF-β2 regulated peroxisome proliferater activated receptor y (PPAR-γ)/platelet derived growth factor β (PDGF-β) signaling pathway in lung fibroblasts of mice.

METHODSC57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-β2, curcumin, or TGF-β2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 μmol/L), the TGF-β2 (10 ng/mL) group, TGF-β2 (10 ng/mL) plus curcumin (5, 25, 50 μmol/L) groups. mRNA expressions of PPAR-γ, platelet-derived growth factor receptor β (PDGFR-β), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-γ and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-β2 group, the TGF-β2 (10 ng/mL) plus curcumin 50 μmol/L group.

RESULTSCompared with the blank control group, curcumin 50 μmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-β2 group, TGF-β2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-γ and PDGF-β, as well as protein expression of PPAR-γ increased, the collagen-1 expression also increased in the TGF-β2 group (P < 0.05). Compared with the TGF-β2 group, mRNA expressions of PPAR-γ obviously increased in the TGF-β2 (10 ng/mL) plus curcumin 25 μmol/L group and the TGF-β2 (10 ng/mL) plus curcumin 50 μmol/L group, higher than that in the TGF-β2 (10 ng/mL) plus curcumin 5 [μmol/L group (P < 0.05). mRNA expressions of PPAR-γ was higher in the TGF-β2 (10 ng/mL) plus curcumin 50 μmol/L group than in the TGF-β2 (10 ng/mL) plus curcumin 25 μmol/L group (P < 0.05). mRNA expressions of PDGF-β was lower in TGF-β2 (10 ng/mL) plus curcumin groups than in the TGF-β2 group (P < 0.05). Besides, PDGF-β mRNA expressions were lower in the TGF-β2 (10 ng/mL) plus curcumin 50 μmol/L group than in the TGF-β2 (10 ng/mL) plus curcumin 5 μmol/L group and the TGF-β2 (10 ng/mL) plus curcumin 25 μmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-β2 group and 3 TGF-β2 plus curcumin groups (P > 0.05). Compared with the TGF-β2 group, PPAR-γ protein expressions increased and collagen-1 protein expressions decreased in the TGF-β2 (10 ng/mL) plus curcumin 50 μLmol/L group (P < 0.05, P < 0.01).

CONCLUSIONSCurcumin not only could inhibit TGF-β2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-γ expressions and down-regulating PDGF-β expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-γ/PDGF-β signaling pathway.

Animals ; Cell Proliferation ; Collagen ; Curcumin ; pharmacology ; Fibroblasts ; metabolism ; Lung ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; PPAR gamma ; metabolism ; RNA, Messenger ; Receptor, Platelet-Derived Growth Factor beta ; metabolism ; Signal Transduction ; Transforming Growth Factor beta ; Transforming Growth Factor beta2 ; metabolism

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved in immune disorders, cancer, asthma, lung fibrosis, and chronic kidney disease, and its signal pathways are considered crucial mediators of a variety of cellular processes. In addition, several recent studies have reported that TGF-beta receptor (TGF-betaR) gene polymorphism is associated with chronic kidney disease. However, the association between end-stage renal disease (ESRD) and the TGF-beta gene polymorphism has not been sufficiently investigated. In this study, we hypothesized that polymorphisms of the TGF-beta ligands or their receptors may be related to ESRD. METHODS: We assessed the relationship between four single-nucleotide polymorphisms (SNPs) in the TGF-betaR2 and TGF-beta2 genes and ESRD, in 312 patients with ESRD and 258 controls. RESULTS: Compared with the control participants, the frequencies of the TGF-betaR2 (rs764522*C) and TGF-betaR2 (rs3087465*G) alleles were significantly higher in the patients with ESRD. Genotyping analysis demonstrated that two SNPs in TGF-betaR2 of the four SNPs included in the study were significantly associated with ESRD in the codominant 1 [rs764522, odds ratio (OR)=1.65; rs3087465, OR=1.63], dominant (rs764522, OR=1.63; rs3087465, OR=1.57), and log-additive (rs764522, OR=1.54; rs3087465, OR=1.39) models after adjusting for age and sex. CONCLUSION: We suggest that TGF-betaR2 polymorphisms (rs764522 and rs3087465) increase the risk of development of ESRD.
Alleles ; Asthma ; Fibrosis ; Humans ; Immune System Diseases ; Kidney Failure, Chronic* ; Ligands ; Lung ; Odds Ratio ; Polymorphism, Single Nucleotide ; Receptors, Transforming Growth Factor beta ; Renal Insufficiency, Chronic ; Signal Transduction ; Transforming Growth Factor beta ; Transforming Growth Factor beta2

BACKGROUND: Capsular contracture is the most troublesome complication in breast implant surgery. Although capsule formation can be seen as a normal reaction to a foreign body, it can induce pain, hardness, deformity, and other pathologic problems. Surgical intervention is required in severe cases, but even surgery cannot guarantee a successful outcome without recurrence. This experimental study confirms that single topical administration of leukotriene antagonist zafirlukast (Accolate, Astrazeneca) reduces peri-implant capsule formation and prevents capsular contracture. METHODS: Twelve smooth-surfaced cohesive gel implants were implanted in New Zealand White rabbits. These miniature implants were designed to be identical to currently used products for breast augmentation. The rabbits were divided into 2 groups. In the experimental group (n=6), the implant and normal saline with zafirlukast were inserted in the submuscular pocket. In the control group (n=6), the implant and normal saline alone were used. Two months later, the implants with peri-implant capsule were excised. We evaluated capsule thickness and collagen pattern and performed immunohistochemical staining of myofibroblasts, transforming growth factor (TGF)-beta1, 2. RESULTS: The thickness of the capsules in the experimental group was reduced in both dorsal and ventral directions. The collagen pattern showed parallel alignment with low density, and the number of myofibroblasts as well as the amounts of TGF-beta1 and TGF-beta2 were reduced in the experimental group. CONCLUSIONS: We suggest that single topical administration of leukotriene antagonist zafirlukast can be helpful in reducing capsule formation and preventing capsular contracture via myofibroblast suppression, modulation of fibroblastic cytokines, and anti-inflammatory effect.
Administration, Topical ; Breast ; Breast Implants ; Capsules ; Collagen ; Congenital Abnormalities ; Contracture ; Cytokines ; Fibroblasts ; Foreign Bodies ; Hardness ; Implant Capsular Contracture ; Myofibroblasts ; Rabbits* ; Recurrence ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factors

BACKGROUND: Certain epidermal appendage tumors, including hyperplasias (hamartomas), adenomas, benign epitheliomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-beta1, TGF-beta2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood. OBJECTIVE: The aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-beta1/beta2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation. METHODS: Immunohistochemistry was performed in follicular and sebaceous tumors using antibodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF-beta1, and TGF-beta2. RESULTS: Gli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differentiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-beta1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation. CONCLUSION: We propose that p63 and/or TGF-beta1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma.
Adenoma ; Antibodies ; Carcinogenesis ; Carcinoma ; Hair ; Humans ; Hyperplasia ; Immunohistochemistry ; Sebaceous Glands ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta2 ; Transforming Growth Factors

PURPOSE: This study was to identify relationships of maternal psychosocial factors including mother's mood state, childcare stress, social support and sleep satisfaction with breastfeeding adaptation and immune substances in breast milk, especially secretory immunoglobulin A (sIgA) and transforming growth factor-beta 2 (TGF-beta2). METHODS: Data were collected from 84 mothers who delivered full-term infants by natural childbirth. Structured questionnaires and breast milk were collected at 2~4 days and 6 weeks postpartum. Data were analyzed using descriptive statistics, Pearson's correlation, multiple linear regression, and generalized estimating equation (GEE). RESULTS: Scores for the breastfeeding adaptation scale were significantly related with child care stress, mood state and social support. Mother's anger was positively correlated with the level of sIgA in colostrum (p<.01). Immune substances of breastmilk was significantly influenced by time for milk collection (p<.001) and the type of breastfeeding (sIgA, p<.001, TGF-beta2, p=.003). Regression analysis showed that breastfeeding adaptation could be explained 59.1% by the type of breastfeeding, childcare stress, the Profile of Mood States, emotional support and sleep quality (F=16.67, p<.001). CONCLUSION: The findings from this study provide important concepts of breastfeeding adaptation program and explanation of psychosocial factors by immune substances in breast milk. Future research, specially, bio-maker research on breast milk should focus on the ways to improve breastfeeding adaptation.
Adaptation, Psychological ; Anger ; Breast Feeding* ; Child ; Child Care ; Colostrum ; Female ; Humans ; Immunoglobulin A, Secretory ; Immunologic Factors ; Infant ; Linear Models ; Milk ; Milk, Human* ; Mothers ; Natural Childbirth ; Postpartum Period ; Pregnancy ; Psychology* ; Surveys and Questionnaires ; Transforming Growth Factor beta2

PURPOSE: This preliminary rabbit study was conducted to evaluate the effect of recombinant human transforming growth factor-beta2 (rhTGF-beta2)/poly lactic-co-glycolic acid (PLGA) coating on osseointegration of the titanium (Ti) implant. MATERIALS AND METHODS: Eight Ti implants were anodized with 300 voltages for three minutes. Four of those were coated with rhTGF-beta2/PLGA by an electrospray method as the experimental group. The implants were placed into tibiae of four New Zealand rabbits, two implants per a tibia, one implant per each group. After 3 and 6 weeks, every two rabbits were sacrificed and micro-computed tomography (microCT) was taken for histomorphometric analysis. RESULTS: In scanning electron microscope (SEM) image, the surface of rhTGF-beta2/PLGA coated Ti implant showed well distributed particles. Although statistically insignificant, microCT analysis showed that experimental group has higher bone volume / total volume (BV/TV) and trabecular thickness (Tb.Th) values relatively. Cross sectional view also showed more newly formed bone in the experimental group. CONCLUSION: In the limitation of this study, rhTGF-beta2/PLGA particles coating on the Ti implant show the possibility of more favorable quantity of newly formed bone after implant installation.
Humans ; Osseointegration* ; Rabbits ; Tibia ; Titanium* ; Transforming Growth Factor beta2 ; X-Ray Microtomography*

OBJECTIVETo investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.

METHODSTwelve 8-week old female C57BL/6 mice were used in this study. The mice were injected with wild-type B16F10 cells through tail vein after immunization with B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine, and the pulmonary metastasis was observed. The CD4(+) and CD8(+) T cells were isolated by magnetic activated cell sorting, and then used for the detection of CFSE/7-AAD cytotoxicity by flow cytometry. Serum from the mice immunized with tumor-cell vaccine was used to detect IFN-γ expression by ELISA. The expression of TGF-β2, ZEB1, E-cadherin, and N-cadherin of tumor tissues was detected by RT-PCR and immunofluorescence, respectively.

RESULTSThe mice vaccinated with B16F10-ESAT-6-gpi/IL-21 had significantly fewer nodules in the lung and lower lung weight [(285.8 ± 19.01) mg vs. (406.3 ± 27.12) mg], with lower levels of TGF-β2, ZEB1 and N-cadherin proteins but higher level of E-cadherin protein within the tumor tissue, as compared with the control mice. Meanwhile, the immunized mice had significantly increased CD8(+) T cell killing activity [(42.62 ± 3.465)% vs. (22.29 ± 1.804)%] and IFN-γ expression level [(55.200 ± 7.173) pg/ml vs. (6.435 ± 1.339) pg/ml] over the control mice.

CONCLUSIONSThe B16F10-ESAT-6-gpi/IL-21 vaccine can inhibit the metastasis of melanoma in the lung in vaccinated melanoma-bearing mice. This inhibitory effect is associated with CD8(+) T cell immune response and a higher level of IFN-γ, which may influence on the mesenchymal-epithelial transition of tumor cells.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Cadherins ; metabolism ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukins ; immunology ; Lung ; pathology ; Lung Neoplasms ; metabolism ; secondary ; Melanoma ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Organ Size ; Transcription Factors ; metabolism ; Transforming Growth Factor beta2 ; metabolism ; Zinc Finger E-box-Binding Homeobox 1