Psoriasis, a chronic, immune-mediated inflammatory disease characterized by hyperproliferation of keratinocytes, is difficult to cure and prone to relapse, often leading to systemic damage. Triptolide (TPL) can modulate cutaneous immune responses and inflammation, yet its therapeutic window is narrow with significant toxicity. To enhance skin targeting and retention of TPL while reducing systemic absorption and toxicity, a TPL/hyaluronic acid/phospholipid polymeric micelle (TPL/HA-DOPE) was constructed via HA's targeting of the CD44 receptor on skin cells. The prepared TPL/HA-DOPE exhibited a uniform spherical morphology with particle size of (130.4±1.23) nm, drug loading capacity of (19.74±0.084) %, and encapsulation efficiency of (85.53±1.34) %. Transdermal permeation studies in vitro and in vivo demonstrated that TPL/HA-DOPE not only enhanced uptake in HaCaT cells but also exhibited excellent skin retention. In a murine model of psoriasis, the TPL/HA-DOPE gel at the dose of 50 μg/(kg•d) showed the most significant improvement in erythema, scaling, and epidermal thickening. Histological analysis confirmed that TPL/HA-DOPE markedly reduced stratum corneum thickness, epidermal hyperplasia, and inflammatory cell infiltration. Ki67 immunostaining proved that its anti-inflammatory mechanism might be achieved by reducing the number of Ki67-positive cells and lowering the levels of inflammatory factors IL-6 and TNF-α. The above results demonstrate that HA-DOPE as a drug delivery carrier for the treatment of psoriasis-like skin diseases has high value of scientific research and good prospects for clinical application.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
Endometriosis/genetics* ; Female ; Animals ; p21-Activated Kinases/genetics* ; Mice ; Phosphorylation ; Glycolysis ; Humans ; Thyroid Hormone-Binding Proteins ; Membrane Proteins/genetics* ; Carrier Proteins/genetics* ; Cell Proliferation ; Mice, Knockout ; Thyroid Hormones/metabolism* ; Pyruvate Kinase/genetics*

3D printing technology has great advantages in small batch and personalized customization, so it has attracted much attention in the biomedical field. The consumables available for 3D printing include polymer, metal, ceramic and derived materials. Biomedical ceramics, with high melting point and poor toughness, are the most difficult materials to be used in 3D printing. The progress of 3D printing ceramic preparation process using ceramic powder, ceramic slurry, ceramic wire, ceramic film and other different raw materials as consumables are reviewed, and the surface roughness, size, density and other parameters of ceramics prepared by SLS, 3DP, DIW, IJP, SL, DLP, FDM, LOM and other different processes are compared. The study also summarizes the clinical application status of 3D printed bioceramics in the field of hard tissue repair such as bone tissue engineering scaffolds and dental prostheses. The SL ceramic additive manufacturing technology based on the principle of UV polymerization has better manufacturing precision, forming quality and the ability to prepare large-size parts, and can also endow bioceramics with better biological properties, mechanical properties, antibacterial, tumor treatment and other functions by doping trace nutrients and surface functional modification. Compared with the traditional subtractive manufacturing process, the bioceramics prepared by 3D printing not only have good mechanical properties, but also often have better biocompatibility and osteoconductivity.
Bone and Bones ; Ceramics ; Printing, Three-Dimensional ; Tissue Engineering ; Tissue Scaffolds

Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.

Objective:To investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on ovarian function and endometrial receptivity in mice with autoimmune premature ovarian insufficiency (POI).Methods:POI mouse was induced by treatment with zona pellucida 3 polypeptide fragment-Freund immune adjuvant. The animals were divided into normal group ( n=10), model group ( n=15) and hAMSCs group ( n=15). hAMSCs (1×10 6 cells/mouse) were transplanted by tail vein single injection. The oestrus cycles were evaluated by vaginal smears. The levels of follicle-stimulating hormone (FSH), estrogen and anti-Müllerian hormone (AMH) in serum were detected by enzyme-linked immunosorbent assay methods. Morphological changes of ovarian and uterus tissues were observed after HE staining. The expressions of homeobox A10 (HOXA10), tumor necrosis factor-α (TNF-α) and FSH receptor (FSHR) proteins in uterine were measured by immunohistochemistry. The endometrial receptivity was comprehensively assessed. Results:After hAMSCs transplanting 6 weeks, the rate of abnormal oestrus cycles in hAMSCs group [40.0% (6/15)] was lower than that in model group [86.7% (13/15), P=0.021]. Compared with the levels of serum FSH [(10.239±1.091) μg/L], estradiol [(103.325±4.952) ng/L] and AMH [(1.133±0.494) μg/L] in model group, the level of FSH in hAMSCs group [(7.664±0.735) μg/L] was significantly decreased ( P<0.001), the levels of estradiol [(126.883±23.370) ng/L] and AMH [(2.204±0.453) μg/L] were significantly increased in hAMSCs group ( P=0.015, P<0.001). Different from model group, the ovarian and uterine index were increased. A large number of healthy follicles at all stages were highly increased, but it was rare to find interstitial fibrosis and atresia follicles. The uterine wall and endometrium were thickened, and the number and volume of the glands were increased. The absorbance ( A) of HOXA10 in hAMSCs group (5.90±1.94) was higher than that in model group (2.79±1.27, P=0.029). The TNF-α A value of hAMSCs (3.83±1.23) group was significantly lower than that of model group (6.26±0.96, P=0.002). Although there was no significant difference on FSHR A value between hAMSCs group (3.61±1.66) and model group (2.74±0.22, P>0.05), the FSHR A value of model group was lower than that of normal group (4.13±0.54, P=0.006). Conclusion:hAMSCs transplantation could restore ovarian function of autoimmune POI mice meanwhile significantly improve uterine receptivity and fertility.

Anatomy is an important medical course for international medical students. In order to improve the teaching quality and enhance the extent of students' learning, teachers integrated the theoretical and experimental courses of systemic anatomy, and introduced the "Digital Human" anatomical system to compensate the shortage of models, so as to realize the integrated theory and experiment teaching of systematic anatomy. Practice indicated that integrated teaching mode of theory and experiment was more consistent with the learning habits of foreign students, which improved their learning effect with significant advantages. But there were still some problems in this teaching mode and measures for solving these problems were proposed in this paper.

Cardiovascular Diseases ; Cardiovascular System ; Circadian Clocks/genetics* ; Circadian Rhythm ; Humans

Since the release rate of protein in hydrogels is directly dependent upon the size of the protein and the hydrogel, how to deliver low molecular weight protein for prolonged periods has always been a problem. In this article, we present a usage of self-assembling peptide (P3) with the RGD epitope on its N terminus. The concentration of the released insulin-like growth factor 1 (IGF-1) was determined by UV-vis spectroscopy and the release kinetics suggested a notable reduction of the IGF-1 release rate. Cell entrapment experiments revealed that IGF-1 delivery by biotinylated nanofibers could promote the proliferation of the mouse chondrogenic ATDC5 cells when compared with cells embedded within nanofibers with untethered IGF-1.
Animals ; Biotin ; Cell Line ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; Hydrogels ; chemistry ; Insulin-Like Growth Factor I ; pharmacology ; Mice ; Nanofibers ; Oligopeptides ; chemistry