Combined Verapamil-Polydopamine Nanoformulation Inhibits Adhesion Formation in Achilles Tendon Injury Using Rat Model.

Introduction: Topical verapamil has been demonstrated to reduce the fibroproliferative scar. Therefore, it was hypothesized that topical verapamil could reduce adhesion formation after tendon repair. The current study aimed to examine the effects of verapamil-loaded polydopamine nanoparticles (VP-PDA NPs) on the adhesion formation of Achilles tendon laceration and repair in a rat model. Methods: We randomly assigned 72 male Sprague-Dawley rats to the control, the PDA NPs, and the VP-PDA NPs groups (n = 24 per group). The quality of tendon healing was evaluated by the maximal tensile strength four and six weeks after surgery. The degree of tendon adhesion was scored on days 4, 15, 29, and 43 after surgery. The expressions of transforming growth factor-beta 1 (TGF-ß1), vimentin, α-smooth muscle actin (α-SMA), and collagens type I and III were detected through Western blotting or immunohistochemistry at four weeks after surgery. Results: In vitro release tests revealed that 61.3% of verapamil was released from VP-PDA NPs in four weeks. There was a significant increase in average failure to load in the VP-PDA NPs group (89.27 ± 5.09 N) compared with the PDA NPs group (65.52 ± 2.04 N) (p = 0.003) and the control group (74.52 ± 4.24 N) (p = 0.029). Adhesion scores were significantly reduced in the VP-PDA NPs group at six weeks (3.175 ± 0.08) and four weeks (3.35 ± 0.25) compared with the other groups. Moreover, VP-PDA NPs significantly reduced the expression of vimentin, α-SMA, TGF-ß1, and collagens type I and III. Conclusion: These data suggest that VP-PDA NPs reduced adhesion formation and enhanced tendon healing during rat tendon injury. Since topical verapamil has been used in clinics without side effects, VP-PDA NPs would have direct translation implications. However, its anti-adhesive effects on intrasynovial tendon injury must be examined.

Retraction Notice to: Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

[This retracts the article DOI: 10.1016/j.omtn.2019.08.010.].

The imbalance of circulating monocyte subgroups with a higher proportion of the CD14+CD16+CD163+ phenotype in patients with preeclampsia.

BACKGROUND: Preeclampsia is a major cause of increased maternal and fetal morbidity and mortality, which is closely related to the abnormal maternal immune response. The skew of decidual macrophage polarization toward M1 phenotype has been proved to promote the pathogenesis of preeclampsia. However, it's not easy to monitor the change of decidual macrophage subtypes. The current study aims to examine the distribution of different circulating monocyte subtypes and analyze whether certain monocyte subtypes act as potential clinical indicators for preeclampsia. METHODS: A total of 50 pregnant women [mild preeclampsia (n = 20); severe preeclampsia (n = 15); healthy pregnancy (n = 15)] and 15 healthy donors were included in the study. Medical information such as BMI, blood pressure, ALT, creatinine, thrombocyte, etc., were recorded. The frequency of different monocyte subtypes in venous blood were measured by flow cytometry. Serum level of IL-6 was detected using Roche-Hitachi cobas 8000. Serum concentration of inflammatory cytokines (IL-1ß, IL-4, IL-10 and TNF-α) were measured by ELISA. RESULTS: A circulating monocyte subset with both M1 and M2 markers (CD14+CD16+CD163+) was found to occupy an obvious higher proportion in the preeclampsia group than in the normal pregnancy group. The ratio of CD206+/CD206- M2-like monocytes was also increased in the preeclampsia group, and meanwhile, it had statistic difference between the mild- and the severe-preeclampsia group. Furthermore, the serum levels of IL-1ß and TNF-α were positively correlated with the frequency of CD14+CD16+CD163+ intermediate monocytes in the preeclampsia group. CONCLUSIONS: The increased proportion of CD14+C16+CD163+ circulating monocytes and the high ratio of CD206+/CD206- M2-like monocytes may act as potential clinical indicators for preeclampsia, with the superiority of convenience and dynamic monitoring.

Epithelioid leiomyosarcoma of the vulva: report of a rare case and literature review.

Leiomyosarcoma of the vulva is a rare soft tissue sarcoma that accounts for approximately 1% of all primary vulvar neoplasms, but it is the most common type of vulvar sarcoma. It usually originates from the smooth muscle within erectile tissue or blood vessel walls, the round ligament, the dartos muscle or the arrector pili muscle. No treatment algorithms have been established to date. Surgical resection is preferred for vulvar leiomyosarcoma. Currently, the recommended surgical method is extensive local resection with a safe surgical margin of at least 2 cm. The use of chemoradiotherapy for vulvar sarcoma remains controversial. This case report describes a 39-year-old female that underwent resection of a vulvar mass in January 2019. Postoperative pathological examination indicated that it was an epithelioid leiomyosarcoma. She presented with tumour recurrence after 43 days. Based on the diagnosis, radical right vulvectomy with a tumour margin of 2 cm was performed. The tumour margin was negative. The patient refused to undergo auxiliary radiotherapy and chemotherapy. The follow-up findings do not indicate any signs of recurrence. In order to avoid recurrence, vulvar epithelioid leiomyosarcomas should be completely resected with a margin of 2 cm at the time of first occurrence.

Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis.

Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.

Conservative treatment of patients with bladder genital tract fistula: Three case reports.

INTRODUCTION: Most of the patients with bladder genital tract fistula recover with surgical treatment. In the present study, we aimed to assess conservative treatment strategies for bladder genital tract fistula. PATIENT CONCERNS: We reviewed 3 cases with bladder genital tract fistula who underwent treatment at our hospital from January to June 2017. Patient 1 underwent cesarean delivery, Patient 2 underwent total abdominal hysterectomy bilateral salpingo-oophorectomy (TAHBSO) and pelvic lymphadenectomy, and Patient 3 underwent extensive TAHBSO and pelvic lymphadenectomy. All 3 patients exhibited involuntary vaginal fluid outflow (average duration, 12.7 days; range, 7-21 days). DIAGNOSIS: Patient 1 was diagnosed as vesicouterine fistula by cystosonography and Patient 2, Patient 3 was diagnosed as vesicovaginal fistula by cystoscopy. INTERVENTIONS: All 3 patients underwent indwelling urinary catheterization. OUTCOMES: No vaginal fluid outflow could be observed after treatment of all 3 patients. CONCLUSION: Indwelling urinary catheterization should be administered for suitable patients as conservative treatment. If vesicouterine fistulas that are simple and have a diameter of <0.5 cm can be treated conservatively. If the condition does not resolve after 2 months, surgery should be considered.

Opportunities and Challenges of the Human Microbiome in Ovarian Cancer.

Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.

miR-214-5p suppresses the proliferation, migration and invasion of trophoblast cells in pre-eclampsia by targeting jagged 1 to inhibit notch signaling pathway.

MicroRNA-214-5p has been reported to be expressed in placental tissue and suppressed the proliferation and invasion of various tumor cells. However, the role of miR-214-5p in pre-eclampsia has not been reported. We aimed to explore the effects of miR-214-5p in proliferation, migration, and invasion of placental trophoblast cells. RT-qPCR was used to quantify the miR-214-5p expression level in placental samples and four types of trophoblast cell lines. Cell proliferation was monitored by CCK-8 and Edu staining assays. Flow cytometry was used to determine the cell cycle. Wound healing and transwell assays were performed to measure the migratory and invasive capacities in JEG-3 and BEWO cells. In addition, we investigated whether miR-214-5p targeted Jagged 1 to regulate the Notch signaling pathway to affect trophoblast cells by luciferase assay and western blot. The expression of miR-214-5p was significantly increased in the placenta of patients with PE. Moreover, the proliferation, migration, and invasion of JEG-3 cells transfected with miR-214-5p mimic were inhibited. The results were reversed when BEWO cells were transfected with miR-214-5p inhibitor. The dual-luciferase assay demonstrated that miR-214-5p directly regulated Jagged 1. The expression of the proteins associated with the Notch signaling pathway, Jagged 1, Notch 1, HEY 1 and HES 1 were all decreased when Jagged 1 was negatively regulated by miR-214-5p. miR-214-5p directly down-regulated Jagged 1 expression, then suppressed proliferation, migration, and invasion of human placental trophoblast cells by inhibiting the Notch signaling pathway.

LncRNA TDRG1/miR-214-5p axis affects preeclampsia by modulating trophoblast cells.

Because of limited treatment options, preeclampsia (PE) is the leading cause of perinatal morbidity and mortality worldwide. Recently, lncRNA TDRG1 is reported to be aberrantly down-regulated in PE placenta, and the abnormal expression of TDRG1 might play a key or partial role in PE development. In this study, we found that TDRG1 was significantly down-regulated in PE placenta compared with the normal placenta. The cell proliferation, migration, invasion, and cell cycle were explored by CCK-8, wound-healing, transwell, and flow cytometer assay, respectively. Experimental results showed that TDRG1 accelerated the proliferation, migration, and invasion of trophoblast cells. Dual-luciferase reporter assays confirmed that TDRG1 could bind to miR-214-5p. Besides, knockdown of TDRG1 suppressed the cell proliferation, migration, and invasion, while knockdown of miR-214-5p reversed the effect. Jagged1 and Notch1 were negatively regulated by miR-214-5p while positively modulated by TDRG1. In conclusion, TDRG1 promoted trophoblast cells viability and invasion by negatively regulating miR-214-5p expression, contributing to a better understanding of PE pathogenesis and providing new light on TDRG1-directed diagnosis and treatment. SIGNIFICANCE OF THE STUDY: In this work, we observed that TDRG1 was able to promote cell proliferation, migration, and invasion cells by suppressing the expression of miR-214-5p and regulating the Notch signalling pathway in trophoblast cells. As far as we know, the effect of TDRG1/miR-214-5p axis on cell viability, migration, and invasion of trophoblast cells was firstly introduced. Our findings provided a better understanding of the mechanism of PE. Moreover, it is reasonable to believe that TDRG1 may be employed as a strategy to treat PE in the future.

Exosomes Derived from miR-143-Overexpressing MSCs Inhibit Cell Migration and Invasion in Human Prostate Cancer by Downregulating TFF3.

Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSC (BMSC)-derived exosomal miR-143 on prostate cancer. During the co-culture experiments, we disrupted exosome secretion by the inhibitor GW4869 and overexpressed exosomal miR-143 using miR-143 plasmid. miR-143 was involved in the progression of prostate cancer via trefoil factor 3 (TFF3). Moreover, miR-143 was downregulated while TFF3 was upregulated in prostate cancer cells and tissues, and miR-143 was found to specifically inhibit TFF3 expression. Human MSC-derived exosomes enriched miR-143 and transferred miR-143 to prostate cancer cells. Furthermore, elevated miR-143 or exosome-miR-143 or silencing TFF3 inhibited the expression of TFF3, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2, and MMP-9 and PC3 cell proliferation, migration, invasion, and tumor growth, whereas it promoted apoptosis. In conclusion, hMSC-derived exosomal miR-143 directly and negatively targets TFF3 to suppress prostate cancer.

Low-dose methotrexate-induced vulvar edema: A case report.

RATIONALE: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate. PATIENT CONCERNS: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp. DIAGNOSES: The patient was diagnosed based on clinical findings for MTX toxic reactions. INTERVENTIONS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed. OUTCOMES: The vulvar edema and oral cavity ulceration and scalp ulceration healed. LESSONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

A case report on Herlyn-Werner-Wunderlich syndrome with spontaneous abortion.

INTRODUCTION: Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital abnormality of the urogenital tract characterized by uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. It is usually diagnosed after menarche, with a clinical presentation of dysmenorrhea, recurrent abdominal pain, and irregular menses. However, it is rare to diagnose it during pregnancy, subsequently resulting in spontaneous abortion. CASE PRESENTATION: A 22-year-old Chinese woman with HWWS whose left uterine pregnancy underwent spontaneous abortion presented with a right perforated obstructed hemivagina and right renal agenesis. The right vaginal septum was resected and the hematocolpos was drained, thereby relieving lower abdominal pain and preserving future fertility. CONCLUSION: Co-presentation of unilateral renal agenesis and uterus didelphys should encourage clinicians to rule out HWWS. Early diagnosis and subsequent treatment can avoid possible serious complications.

Piperine ameliorates collagenase-induced Achilles tendon injury in the rat.

Tendinopathy is a common clinical pathology found in athletes and workers with mixed treatment results. Piperine, a major alkaloid found in the black and long pepper, has been demonstrated to have variety of pharmacological properties such as analgesic and anti-inflammatory effects. The present study was designed to investigate the effects of piperine on collagenase-induced Achilles tendon injury. Rats were intratendineously injected with collagenase in the right Achilles tendon, followed by intragastrical administration of piperine (100 mg/kg). Morphological structure and biochemical analysis of glycosaminoglycans, hydroxyproline, collagen III, and the activity of matrix metallopeptidases in the tendon tissues were performed. Our results showed that collagenase injection resulted in clear degenerative changes in the tendon. Administration of piperine improved the morphological structure of tendon, increased glycosaminoglycans and hydroxyproline levels, and inhibited the expression and activities of MMP-2 and MMP-9. Furthermore, piperine inhibited the activation of ERK and p38 signaling pathways in injured tendon. These results indicate a beneficial role of piperine against collagenase-induced tendon injury.

MicroRNA-210 contributes to peripheral nerve regeneration through promoting the proliferation and migration of Schwann cells.

Peripheral nerve injury impacts the daily life of affected individuals. MicroRNA (miR)-210 is a multifunctional miR and has effects on the proliferation, migration and differentiation of cells. However, whether miR-210 has effects on peripheral nerve regeneration has remained elusive. In the present study, the miR-210 levels in a rat model of sciatic nerve injury were evaluated by reverse-transcription quantitative PCR and the effects of miR-210 on the proliferation and migration of Schwann cells were explored. Elevated miR-210 levels were discovered in the sciatic nerve injury rat model. miR-210 mimics were found to promote the proliferation and migration of Schwann cells, while miR-210 inhibitor was found to inhibit the proliferation and migration of Schwann cells. Further study showed that miR-210 had effects on the expression of growth-associated protein-43, myelin-associated glycoprotein and myelin basic protein. These results showed that miR-210 had effects on the proliferation and migration of Schwann cells and may be involved in the peripheral nerve regeneration.

Multiple primary cancer in the female genital system: Two rare case reports and a literature review.

RATIONALE: Multiple primary cancer (MPC) refers to tumors that occur in one or multiple organs within the same patient at the same time or at different periods. MPC often occurs in the head and neck, but is rarely reported in the female genital system. PATIENT CONCERNS: In the present study, we report 2 rare cases that presented with tangible lower abdominal tumors. DIAGNOSES: Laboratory tests, pelvic ultrasound (US), computed tomography (CT), and fast histopathological examinations during surgery indicated a diagnosis of MPC. INTERVENTIONS: The 2 patients all received radical resections of multiple tumors. OUTCOMES: Postsurgical histopathological and immunohistochemical examinations further confirmed primary endometrial cancer and right ovarian cancer in Case 1, and primary cervical cancer and left ovarian cancer of Case 2. The 2 patients all recovered well without obvious complications. LESSONS: Our study demonstrated that female genital MPC should be noted for patients with multiple genital tumors. In addition, accurately diagnosis and radical surgical treatment should be well performed.