Double-Network DNA Macroporous Hydrogel Enables Aptamer-Directed Cell Recruitment to Accelerate Bone Healing.

Recruiting endogenous bone marrow mesenchymal stem cells (BMSCs) in vivo to bone defect sites shows great promise in cell therapies for bone tissue engineering, which tackles the shortcomings of delivering exogenous stem cells, including limited sources, low retention, stemness loss, and immunogenicity. However, it remains challenging to efficiently recruit stem cells while simultaneously directing cell differentiation in the dynamic microenvironment and promoting neo-regenerated tissue ingrowth to achieve augmented bone regeneration. Herein, a synthetic macroporous double-network hydrogel presenting nucleic acid aptamer and nano-inducer enhances BMSCs recruitment, and osteogenic differentiation is demonstrated. An air-in-water template enables the rapid construction of highly interconnective macroporous structures, and the physical self-assembly of DNA strands and chemical cross-linking of gelatin chains synergistically generate a resilient double network. The aptamer Apt19S and black phosphorus nanosheets-specific macroporous hydrogel demonstrate highly efficient endogenous BMSCs recruitment, cell differentiation, and extracellular matrix mineralization. Notably, the enhanced calvarial bone healing with promising matrix mineralization and new bone formation is accompanied by adapting this engineered hydrogel to the bone defects. The findings suggest an appealing material approach overcoming the traditional limitations of cell-delivery therapy that can inspire the future design of next-generation hydrogel for enhanced bone tissue regeneration.

Ferroptosis in epithelial ovarian cancer: a burgeoning target with extraordinary therapeutic potential.

Epithelial ovarian cancer (EOC) is universally acknowledged as a terrifying women killer for its high mortality. Recent research advances support that ferroptosis, an emerging iron-dependent type of regulated cell death (RCD) triggered by the excessive accumulation of lipid peroxides probably possesses extraordinary therapeutic potential in EOC therapy. Herein, we firstly provide a very concise introduction of ferroptosis. Special emphasis will be put on the ferroptosis's vital role in EOC, primarily covering its role in tumorigenesis and progression of EOC, the capability of reversing chemotherapy resistance, and the research and development of related therapeutic strategies. Furthermore, the construction of ferroptosis-related prognostic prediction systems, and mechanisms of ferroptosis resistance in EOC are also discussed. Finally, we propose and highlight several important yet unanswered problems and some future research directions in this field.

Amyloid Fibril and Clay Nanosheet Dual-Nanoengineered DNA Dynamic Hydrogel for Vascularized Bone Regeneration.

Dynamic hydrogels have attracted enormous interest for bone tissue engineering as they demonstrate reversible mechanics to better mimic biophysical cues of natural extracellular matrix (ECM) compared to traditional static hydrogels. However, the facile development of therapeutic dynamic hydrogels that simultaneously recapitulate the filamentous architecture of the ECM of living tissues and induce both osteogenesis and angiogenesis to augment vascularized bone regeneration remains challenging. Herein, we report a dual nanoengineered DNA dynamic hydrogel developed through the supramolecular coassembly of amyloid fibrils and clay nanosheets with DNA strands. The nanoengineered ECM-like fibrillar hydrogel network is facilely formed without a complicated and tedious molecular synthesis. Amyloid fibrils together with clay nanosheets synergistically enhance the mechanical strength and stability of the dynamic hydrogel and, more remarkably, endow the matrix with an array of tunable features, including shear-thinning, injectability, self-healing, self-supporting, and 3D printable properties. The QK peptide is further chemically grafted onto amyloid fibrils, and its sustainable release from the hydrogel matrix stimulates the tube formation and migration with human umbilical vein endothelial cells. Meanwhile, the nanoengineered hydrogel matrix promotes osteogenic differentiation of bone marrow mesenchymal stem cells due to the sustainable release of Si4+ and Mg2+ derived from clay nanosheets. Furthermore, the manipulation of enhanced vascularized bone regeneration by the dynamic hydrogel is revealed in a rat cranial bone defect model. This dual nanoengineered strategy envisions great promise in developing therapeutic dynamic hydrogels for improved and customizable bone regeneration.

Methyl vanillate for inhibiting the proliferation, migration, and epithelial-mesenchymal transition of ovarian cancer cells via the ZEB2/Snail signaling pathway.

Background: Globally, ovarian cancer is the leading cause of female reproductive-related death, with a 5-year survival rate below 50%. Conventional therapies, such as cancer cell reduction and paclitaxel chemotherapy, have strong toxicity and are prone to drug resistance. Thus, the development of alternatives for the treatment of ovarian cancer is urgently needed. Methyl vanillate is a principal component of Hovenia dulcis Thunberg. It is known that several cancer cells are inhibited by methyl vanillate; however, whether methyl vanillate can inhibit the proliferation and migration of ovarian cancer cells still needs to be further studied. Methods: In this study, cell counting kit 8 (CCK8) was used to examine the effects of methyl vanillic acid on the proliferation of SKOV3 cell lines and human ovarian surface epithelial cell (HOSEpiC) lines. Wound healing and transwell assays were used to determine the effect of methyl vanillate on cell migration. The expression of epithelial-mesenchymal transition (EMT) marker proteins (E-cadherin and vimentin), transcription factors (Snail and ZEB2), and skeletal proteins (F-actin) were evaluated with Western blotting. F-actin was detected by immunofluorescence assay. Results: The proliferation and migration of SKOV3 cells were dose-dependently inhibited by methyl vanillate, but HOSEpiC cells were not inhibited by low concentrations of methyl vanillate. Western blotting analyses revealed a significant decrease in the expression of vimentin and a significant increase in the expression of E-cadherin in SKOV3 cells treated with methyl vanillate. This finding indicated that EMT inhibition was induced by the vanillate. Furthermore, methyl vanillate inhibited the expression of transcription factors (Snail and ZEB2) in SKOV3 cells as well as cytoskeletal F-actin assembly. Conclusions: Methyl vanillate plays an important role in inhibiting EMT and cell proliferation and the migration of ovarian cancer, likely via the inhibition of the ZEB2/Snail signaling pathway. Consequently, methyl vanillate may be a promising therapeutic drug for ovarian cancer.

scRNA-seq reveals aging-related immune cell types and regulators in vaginal wall from elderly women with pelvic organ prolapse.

Introduction: In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences. Methods: Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing. Results: The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging. Conclusions: Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.

Prussian Blue Nanoparticle-Entrapped GelMA Gels Laden with Mesenchymal Stem Cells as Prospective Biomaterials for Pelvic Floor Tissue Repair.

Pelvic organ prolapse (POP) seriously affects elderly patients' quality of life, and new repair materials are urgently needed. To solve this problem, we synthesized methacrylated gelatin (GelMA) hydrogels and incorporated photothermally active Prussian blue nanoparticles (PBNPs) to synthesize PBNP@GelMA. Then, MSCs were encapsulated in the PBNP@GelMA and exposed to a 1.0 W/cm2 of 808 nm laser for 10 min to perform heat shock pretreatment for the implantation of mesenchymal stem cells (MSCs). Next, we tested the repair efficacy of scaffold-cell complexes both in vitro and in vivo. Our results reveal that the heat shock treatment induced by PBNP@GelMA improved the viability of MSCs, and the underlying mechanism may be related to HSP70. Furthermore, 2 weeks after implantation in the SD rat model, the collagen content increased in the MSC implantation group and PBNP@GelMA implantation group. However, the muscle regeneration at the implanting position was mostly enhanced after the implantation of the heat-shock-pretreated MSCs, which illustrates that heat shock treatment can further promote the MSC-mediated muscle regeneration. Therefore, manipulating the cell environment and providing proper heat stimulus by using PBNP@GelMA with NIR is a novel strategy to enhance the regenerative potential of MSCs and to promote pelvic tissue repair.

Current practice in animal models for pelvic floor dysfunction.

INTRODUCTION AND HYPOTHESIS: The objective was to explore the current practice of using animal models for female pelvic floor dysfunction (PFD). METHODS: By applying PFD and animal models as the keywords, we made a computerized search using PubMed, Ovid-Medline and Ovid-Embase from 2000 to 2022. The publications on the construction and application of animal models for PFD were included, and the results are presented in narrative text. RESULTS: Studies on PFD primarily use rodents, large quadrupeds, and nonhuman primates (NHPs). NHPs are closest to humans in anatomy and biomechanics of the pelvic floor, followed by large quadrupeds and rodents. Rodents are more suitable for studying molecular mechanism, histopathology of PFD, and mesh immune rejection. Large quadrupeds are adaptable to the study of pelvic floor biomechanics and the development of new surgical instruments for PFD. NHPs are suitable for studying the occurrence and pathogenesis of pelvic organ prolapse. Among modeling methods, violent destruction of pelvic floor muscles, regulation of hormone levels, and denervation were used to simulate the occurrence of PFD. Gene knockout can be used to study both the pathogenesis of PFD and the efficacy of treatments. Other methods such as abdominal wall defect, vaginal defect, and in vitro organ bath system are more frequently used to observe wound healing after surgery and to verify the efficacy of treatments. CONCLUSIONS: The rat is currently the most applicable animal type for numerous modeling methods. Vaginal dilation is the most widely used modeling method for research on the pathogenesis, pathological changes, and treatment of PFD.

Black phosphorus nanosheets-enabled DNA hydrogel integrating 3D-printed scaffold for promoting vascularized bone regeneration.

The classical 3D-printed scaffolds have attracted enormous interests in bone regeneration due to the customized structural and mechanical adaptability to bone defects. However, the pristine scaffolds still suffer from the absence of dynamic and bioactive microenvironment that is analogous to natural extracellular matrix (ECM) to regulate cell behaviour and promote tissue regeneration. To address this challenge, we develop a black phosphorus nanosheets-enabled dynamic DNA hydrogel to integrate with 3D-printed scaffold to build a bioactive gel-scaffold construct to achieve enhanced angiogenesis and bone regeneration. The black phosphorus nanosheets reinforce the mechanical strength of dynamic self-healable hydrogel and endow the gel-scaffold construct with preserved protein binding to achieve sustainable delivery of growth factor. We further explore the effects of this activated construct on both human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs) as well as in a critical-sized rat cranial defect model. The results confirm that the gel-scaffold construct is able to promote the growth of mature blood vessels as well as induce osteogenesis to promote new bone formation, indicating that the strategy of nano-enabled dynamic hydrogel integrated with 3D-printed scaffold holds great promise for bone tissue engineering.

Bone tissue engineering scaffolds with HUVECs/hBMSCs cocultured on 3D-printed composite bioactive ceramic scaffolds promoted osteogenesis/angiogenesis.

Background: /Objective: Tissue engineering involves scaffolds, cells and growth factors, among which growth factors have limited applications due to potential safety risks and high costs. Therefore, an alternative approach to exogenously induce osteogenesis is desirable. Considering that osteogenesis and angiogenesis are coupled, a system of human umbilical vein endothelial cells (HUVECs) and human bone mesenchymal stem cells (hBMSCs) coculture is more biologically adapted to the microenvironment in vivo and can mediate osteogenesis and angiogenesis via paracrine signalling. Hence, in this study, a HUVECs/hBMSCs coculture system with appropriate cell and medium proportions was established. The substrate for the coculture system was a 3D-printed composite bioceramic scaffold (ß-TCP/CaSiO3) based on a previous study. The aim of this study was to explore the potential of this system for bone tissue engineering. Methods: Bioactive ceramic scaffolds for tissue engineering were fabricated via a 3D Bioplotter™ system. The coculture system for in vitro and in vivo studies consisted of direct contact between HUVECs and hBMSCs cultured on the 3D-printed scaffolds. Results: The proportions of HUVECs/hBMSCs and medium components were determined by cell viability, and the coculture system showed negligible cytotoxicity. CD31 secreted by HUVECs formed strings, and cells tended to aggregate in island chain-like arrays. Real-time cell tracking showed that HUVECs were recruited by hBMSCs, and the integrin expression by HUVECs was upregulated. Ultimately, osteogenic and angiogenic marker gene expression and protein secretion were upregulated. Moreover, the obtained bone tissue engineering scaffolds could induce early osteogenic protein secretion and capillary tube formation in nude rats. Conclusion: These bone tissue engineering scaffolds without exogenous growth factors exhibited the ability to promote osteogenesis/angiogenesis. Translational potential of this article: The fabricated 3D-printed bioactive ceramic scaffolds could provide mechanical, biodegradable and bioadaptive support for personalized bone regeneration. In addition, the bone tissue engineering scaffolds exhibited the ability to promote osteogenesis/angiogenesis without the addition of exogenous growth factors, thus mitigating safety risks. Although application of the HUVECs/hBMSCs coculture system might be a time-consuming process, further development of cord blood storage could be beneficial for multicell coculture.

3D-printed bioactive ceramic scaffolds with biomimetic micro/nano-HAp surfaces mediated cell fate and promoted bone augmentation of the bone-implant interface in vivo.

Calcium phosphate bio-ceramics are osteo-conductive, but it remains a challenge to promote the induction of bone augmentation and capillary formation. The surface micro/nano-topography of materials can be recognized by cells and then the cell fate are mediated. Traditional regulation methods of carving surface structures on bio-ceramics employ mineral reagents and organic additives, which might introduce impurity phases and affect the biological results. In a previous study, a facile and novel method was utilized with ultrapure water as the unique reagent for hydrothermal treatment, and a uniform hydroxyapatite (HAp) surface layer was constructed on composite ceramics (ß-TCP/CaSiO3) in situ. Further combined with 3D printing technology, biomimetic hierarchical structure scaffolds were fabricated with interconnected porous composite ceramic scaffolds as the architecture and micro/nano-rod hybrid HAp as the surface layer. The obtained HAp surface layer favoured cell adhesion, alleviated the cytotoxicity of precursor scaffolds, and upregulated the cellular differentiation of mBMSCs and gene expression of HUVECs in vitro. In vivo studies showed that capillary formation, bone augmentation and new bone matrix formation were upregulated after the HAp surface layer was obtained, and the results confirmed that the fabricated biomimetic hierarchical structure scaffold could be an effective candidate for bone regeneration.

A rare case of nevus sebaceous of the bilateral labia minora: A case report and review of literature.

RATIONALE: Nevus sebaceous (NS) is a lesion caused by congenital hyperplastic disorder of the sebaceous glands. It commonly noted in the scalp and face and rarely in the trunk, neck, or oral mucosa. We present a rare case of a lesion arising in the genital region. PATIENT CONCERNS: A 47-year-old woman complained of a gradual increase in the size of her bilateral labia minora over 2 years, which affected her sexual life and caused walking difficulty. She was admitted to the Department of Obstetrics and Gynecology. On physical examination, no ulcer, discharge, and vulval or vaginal bleeding were found. The bilateral inguinal lymph nodes were not palpable, bilateral labia minora were asymmetric, and the right side was evidently bigger than the left. The labia minora had serrated edges and numerous papillae with a maximum diameter of 0.5 cm. The vagina, cervix, and uterus with its attachments were normal. Blood samples tested negative for human immunodeficiency virus, human papilloma virus, hepatitis B virus, and hepatitis C virus. DIAGNOSIS: A diagnosis of NS of the bilateral labia minora was made following histopathological examination of the resected specimen. INTERVENTION: The bilateral labia minora lesions were resected general anesthesia on August 29, 2016. The operation was successful, and intraoperative blood loss was about 10 ml. OUTCOMES: After 40 months of postoperative follow-up, no recurrence or appearance of other tumors were noted. LESSONS: We recommend surgical removal of lesions in the genital area during adolescence or before adulthood. Adolescence may be the best period for surgical intervention owing to a greater risk of malignant change in adulthood. On the other hand, surgical risk should be avoided in children considering the low incidence of malignant transformation.

Impact of obesity on operative complications and outcome after sacrocolpopexy: A systematic review and meta-analysis.

OBJECTIVE: Surgery is required by many obese women with pelvic organ prolapse, and sacrocolpopexy is considered to be an effective method to correct apical prolapse. However, to the authors' knowledge, epidemiological studies have not been summarized formally. STUDY DESIGN: A systematic literature search of Pubmed, Medline (Ovid) and Embase databases was undertaken for articles written in English. Statistical analysis was performed using Revman 5.3. RESULTS: In total, 7315 patients in 12 studies were included in this meta-analysis. No significant differences were found between obese women and non-obese women in terms of re-operation rate [risk ratio (RR) 1.19, 95 % confidence interval (CI) 0.88-1.59; p = 0.25], postoperative Pelvic Organ Prolapse Quantification System stage ≥2 (RR 0.86, 95 % CI 0.64-1.16; p = 0.33), transfusion rate (RR 0.91, 95 % CI 0.57-1.44; p = 0.68), mesh erosion rate (RR 1.62, 95 % CI 0.74-3.51; p = 0.23), overall rate of surgical complications (RR 1.17, 95 % CI 0.91-1.50; p = 0.23) and length of hospital stay [mean difference (MD) 0.13 days, 95 % CI -0.05 to 0.31; p = 0.15). Additionally, no differences were found in the rates of bladder injury, ileus and urinary incontinence between obese women and non-obese women. However, obese women were associated with a higher laparoconversion rate (RR 3.00, 95 % CI 1.71-5.31; p = 0.0002), higher rate of infection (RR 1.65, 95 % CI 1.25-2.20; p = 0.0005), longer operative duration (MD 14.93 min, 95 % CI 10.14-19.73; p < 0.00001) and higher estimated blood loss (MD 18.01 ml, 95 % CI 8.22-27.80; p = 0.0003) compared with non-obese women. CONCLUSIONS: The complications and curative effects of sacrocolpopexy for obese women are similar to those of non-obese women, except for the higher laparoconversion rate, higher rate of infection, longer operative duration and higher estimated blood loss in obese women. Obesity increases the operational difficulty of sacrocolpopexy to a certain extent, although it does not increase the mesh erosion rate or prolapse recurrence rate. Gynaecologists need to be aware of the possibility of the abovementioned risks when choosing sacrocolpopexy for obese patients with middle pelvic defects.

Agrin promotes the proliferation, invasion and migration of rectal cancer cells via the WNT signaling pathway to contribute to rectal cancer progression.

Rectal cancer is the most common malignant tumor in the digestive system with rapidly metastasis and highly recurrence. Agrin (AGRN) is a proteoglycan involving in a large number of human cancers. However, how AGRN regulates the progression of rectal cancer remains largely unknown. We aimed to determine the biological role of AGRN and its mechanism in rectal cancer. AGRN expression in rectal cancer tissues was detected based on TCGA. The survival curve was plotted using the Kaplan-Meier method. qRT-PCR and western blot were utilized to examine the expression level of AGRN in cells. Cell proliferation, clonogenic ability, invasion, and migration of rectal cancer cells were analyzed by CCK-8, colony formation and transwell experiments. GSEA was employed for the analysis of the potential pathways-related with AGRN in rectal cancer. The activity of WNT pathway was determined by western blot. AGRN expression was dramatically increased in rectal cancer, and its up-regulation was associated with poorer prognosis of rectal cancer patients. AGRN expression was an independent factor for the prognosis of rectal cancer. AGRN inhibition suppressed rectal cancer cell growth, invasion, and migration, whereas AGRN overexpression facilitated these behaviors of rectal cancer cells in vitro. Mechanistically, WNT signaling pathway was enriched in high AGRN-expressing patients with rectal cancer. AGRN elevated the activity of WNT pathway through increasing Cyclin D1, C-Myc, p-GSK-3ß, and p-ß-catenin expression. Our present study indicated that AGRN might function as an oncogenic indicator in rectal cancer via activating the WNT pathway, which would help develop optimized therapeutic therapies for rectal cancer.

The Fractional CO2 Laser for the Treatment of Genitourinary Syndrome of Menopause: A Prospective Multicenter Cohort Study.

BACKGROUND AND OBJECTIVES: Genitourinary syndrome of menopause (GSM) is a common condition affecting of most postmenopausal women, which greatly impacks the quality of life,and need to treat. This prospective multicenter cohort study aimed to compare the efficacy and safety of the fractional carbon dioxide (CO2 ) laser with that of topical estrogen for vaginal treatment and relieving symptoms of genitourinary syndrome of menopause (GSM). STUDY DESIGN/MATERIALS AND METHODS: This study included 162 postmenopausal patients who received vaginal laser or topical Estriol cream therapy between January 2017 and May 2019 at eight study centers in China. The degree of GSM-related symptoms (vaginal burning, dryness, and dyspareunia) was evaluated using the Vaginal Health Index score (VHIS) and Visual Analog Scale (VAS) at baseline, 1, 3, 6, and 12 months posttreatment. The primary endpoint was the improvement in vaginal burning, dryness, and dyspareunia at 6 months after treatment. Multivariate logistic regression was used to compare the rate of improvement in the two groups. RESULTS: At baseline, the laser and control groups showed no significant difference in the mean age, time after menopause, and the VHIS (all P > 0.05). In the laser group, compared with baseline, significant differences were seen in the VHIS after the first or second treatment session and at 1, 3, 6, and 12 months posttreatment (P < 0.01). In the control group, compared with baseline, the VHIS showed significant differences after 1, 3, and 6 months of treatment (P < 0.05). However, there was no significant difference after 3 and 6 months of follow-up between the two groups (P > 0.05). The VHIS scores were significantly higher after 1 month (16.63 ± 2.79 vs. 15.57 ± 2.43) and 12 months (15.72 ± 2.59 vs. 12.12 ± 4.08) of treatment in both the groups (P < 0.05). At 6 months after treatment, both groups showed improvement in vaginal burning, vaginal dryness, and dyspareunia (P > 0.05). The VAS findings at 6 months posttreatment were significantly different when compared with the pretreatment findings (P < 0.001). There were no significant adverse effects in the two groups. CONCLUSIONS: Fractional CO2 laser vaginal treatment could be a safe and effective option for treating symptoms of GSM, including vaginal burning, dryness, and dyspareunia. The improvement in symptoms was comparable with that seen with topical estrogen therapy and lasted for at least 6-12 months posttreatment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Cellular senescence: A pathogenic mechanism of pelvic organ prolapse (Review).

Pelvic organ prolapse (POP) is a common symptom of pelvic floor disorders which is characterized by the descent of the uterus, bladder or bowel from their normal anatomical position towards or through the vagina. Among the older population, the incidence of POP increases with age. It is becoming necessary to recognize that POP is a degenerative disease that is correlated with age. In recent years, studies have been performed to improve understanding of the cellular and molecular mechanisms concerning senescent fibroblasts in pelvic tissues, which contribute to the loss of structure supporting the pelvic organs. These mechanisms can be classified into gene and mitochondrial dysfunctions, intrinsic senescence processes, protein imbalance and alterations in stem cells. The present review provides an integrated overview of the current research and concepts regarding POP, in addition to discussing how fibroblasts can be targeted to evade the negative impact of senescence on POP. However, it is probable that other mechanisms that can also cause POP exist during cell senescence, which necessitates further research and provides new directions in the development of novel medical treatment, stem cell therapy and non­surgical interventions for POP.

Status, challenges, and future prospects of stem cell therapy in pelvic floor disorders.

Pelvic floor disorders (PFDs) represent a group of common and frequently-occurring diseases that seriously affect the life quality of women, generally including stress urinary incontinence and pelvic organ prolapse. Surgery has been used as a treatment for PFD, but almost 30% of patients require subsequent surgery due to a high incidence of postoperative complications and high recurrence rates. Therefore, investigations of new therapeutic strategies are urgently needed. Stem cells possess strong multi-differentiation, self-renewal, immunomodulation, and angiogenesis abilities and they are able to differentiate into various cell types of pelvic floor tissues and thus provide a potential therapeutic approach for PFD. Recently, various studies using different autologous stem cells have achieved promising results by improving the pelvic ligament and muscle regeneration and conferring the tissue elasticity and strength to the damaged tissue in PFD, as well as reduced inflammatory reactions, collagen deposition, and foreign body reaction. However, with relatively high rates of complications such as bladder stone formation and wound infections, further studies are necessary to investigate the role of stem cells as maintainers of tissue homeostasis and modulators in early interventions including therapies using new stem cell sources, exosomes, and tissue-engineering combined with stem cell-based implants, among others. This review describes the types of stem cells and the possible interaction mechanisms in PFD treatment, with the hope of providing more promising stem cell treatment strategies for PFD in the future.

Phosphorylated Chitosan Hydrogels Inducing Osteogenic Differentiation of Osteoblasts via JNK and p38 Signaling Pathways.

Phosphorous-containing biopolymers have been applied to expedite the regeneration of damaged bone tissue by stimulating the function of phosphorous groups in natural bones. However, the underlying mechanism of phosphorous-containing biopolymers in promoting osteogenic differentiation is unclarified. Herein, we synthesized phosphorylated chitosan hydrogels by incorporating phosphocreatine into chitosan molecular chains under mild conditions. The introduction of phosphate groups improved properties of protein adsorption and calcium deposition without affecting the morphology of hydrogels. Our results showed that phosphorylated chitosan hydrogels could not only promote alkaline phosphatase activity and mineralization but also upregulate the expression of osteogenic-related genes and proteins. Meanwhile, application of c-Jun N-terminal kinase inhibitor SP600125 and p38 mitogen-activated protein kinase inhibitor SB203580 repressed the expression of osteogenic-related markers in gene and protein levels. To the best of our knowledge, it is reported for the first time that phosphorous-containing biopolymers promote osteogenic differentiation of osteoblasts via JNK and p38 signaling pathways.

Diagnostic value of pelvic floor ultrasonography for diagnosis of pelvic organ prolapse: a systematic review.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) is a common medical condition universally. In addition to physical examination, experts have increasingly turned their attention to ultrasound in diagnosing POP for its low cost and dynamic imaging. The aim of this paper is to provide an overview of the methods of pelvic floor ultrasound in diagnosing POP, which has been lacking up till now. METHODS: We included original papers comparing the outcome of the Pelvic Organ Prolapse Quantification system and ultrasound, published from 2008 to present in English, using electronic databases (MEDLINE, EMBASE, CENTRAL, PUBMED). All stages of the review were conducted in parallel by two reviewers. RESULTS: Fifteen papers were included. We found that current methods have advantages and limitations. The main methods are to measure levator hiatus-related parameters and distances between the lowest point of the pelvic organs and reference lines during Valsalva maneuver, contraction, and at rest. CONCLUSIONS: Pelvic floor ultrasound is valuable in diagnosing POP, yet suffers from a weakness in precision compared with physical examination. From the existing research, we found that the differences in baseline data such as weight, height, ethnicity, etc., may affect the cutoffs of the above-mentioned parameters. Further research is required to find one appropriate cutoff for each parameter, even if it is necessary to set group values for every parameter according to varying situations.

IL-8 promotes cell migration through regulating EMT by activating the Wnt/ß-catenin pathway in ovarian cancer.

Interleukin-8 (IL-8), as an inflammatory chemokine, has been previously shown to contribute to tumorigenesis in several malignancies including the ovarian cancer. However, little is known about how IL-8 promotes the metastasis and invasion of ovarian cancers cells. In this study, we found that IL-8 and its receptors CXCR1 and CXCR2 were up-regulated in advanced ovarian serous cancer tissues. Furthermore, the level of IL-8 and its receptors CXCR1 and CXCR2 expression were associated with ovarian cancer stage, grade and lymph node metastasis. In vitro, IL-8 promoted ovarian cancer cell migration, initiated the epithelial-mesenchymal transition (EMT) program and activated Wnt/ß-catenin signalling. However, when treated with Reparixin (inhibitor of both IL-8 receptors CXCR1 and CXCR2), effect of both endogenous and exogenous IL-8 was reversed. Together, our results indicated that IL-8 triggered ovarian cancer cells migration partly through Wnt/ß-catenin pathway mediated EMT, and IL-8 may be an important molecule in the invasion and metastasis of ovarian cancer.

Engineering natural matrices with black phosphorus nanosheets to generate multi-functional therapeutic nanocomposite hydrogels.

Natural polysaccharides and proteins have been widely explored for the preparation of hydrogel matrices due to their promising biocompatibility and biodegradability. However, it is challenging to achieve multiple functions of the hydrophilic matrix through convenient functionalization strategies. Herein we report the facile engineering of a natural matrix with black phosphorus (BP) nanosheets as building blocks to generate a therapeutic nanocomposite hydrogel (BP/Gel) with an array of promising features. BP nanosheets could reinforce the crosslinking networks and significantly promote their capabilities of mineralization. The BP/Gel nanocomposite hydrogel exhibits excellent near infrared (NIR) photothermal performance and good biocompatibility in vitro and in vivo. Upon NIR irradiation, the nanocomposite hydrogel demonstrates efficient photothermal antibacterial features. More remarkably, the BP nanosheet engineered hydrogel matrix is capable of promoting in vitro osteogenesis in the absence of osteoinductive factors, and in the meantime demonstrates significant newborn cranial bone tissue formation in a Sprague-Dawley rat model. These results demonstrate that BP nanosheets could endow the natural matrix with multiple functions including reinforced networks, photothermal performance, enhanced mineralization and bone regeneration, which provides a facile and highly efficient therapeutic strategy for bone tissue engineering.