Aim Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE. Methods The published articles were reviewed. Results The prevalence of CE has been found to be 2.8–56.8% in infertile women, 14–67.5% in women with recurrent implantation failure (RIF), and 9.3–67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE. Conclusion CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.
Preferential accumulation of nanoparticles in a tumor is realized commonly by combined effects of active and passive targeting. However, passive targeting based on an enhanced permeation and retention (EPR) effect is not sufficient to observe clear tumor fluorescence images in most of the in vivo experiments using tumor‐bearing mice. Herein, polyglycerol‐functionalized nanodiamonds (ND‐PG) conjugated with cyanine dye (Cy7) are synthesized and it is found that the resulting ND‐PG‐Cy7 is preferentially accumulated in the tumor, giving clear fluorescence in in vivo and ex vivo fluorescence images. One of the plausible reasons is the longer in vivo blood circulation time of ND‐PG‐Cy7 (half‐life: 58 h determined by the pharmacokinetic analysis) than that of other nanoparticles (half‐life: <20 h in most of the previous reports). In a typical example, the fluorescence intensity of tumors increases due to continuous tumor accumulation of ND‐PG‐Cy7, even more than one week postinjection. This may be owing to the stealth effect of PG that was reported previously, avoiding recognition and excretion by reticuloendothelial cells, which are abundant in liver and spleen. In fact, the fluorescence intensities from the liver and spleen is similar to those from other organs, while the tumor exhibits much stronger fluorescence in the ex vivo image.
Background The diagnostic criteria of chronic endometritis remain controversial in the treatment for infertile patients. Methods A prospective observational study was conducted in a single university from June 2014 to September 2017. Patients who underwent single frozen-thawed blastocyst transfer with a hormone replacement cycle after histological examination for the presence of chronic endometritis were enrolled. Four criteria were used to define chronic endometritis according to the number of plasma cells in the same group of patients: 1 or more (≥ 1) plasma cells, 2 or more (≥ 2), 3 or more (≥ 3), or 5 or more (≥ 5) in 10 high-power fields. Pregnancy rates, live birth rates, and miscarriage rates of the non-chronic endometritis and the chronic endometritis groups defined with each criterion were calculated. A logistic regression analysis was performed for live births using eight explanatory variables (seven infertility factors and chronic endometritis). A receiver operating characteristic curve was drawn and the optimal cut-off value was calculated. Results A total of 69 patients were registered and 53 patients were finally analyzed after exclusion. When the diagnostic criterion was designated as the presence of ≥ 1 plasma cell in the endometrial stroma per 10 high-power fields, the pregnancy rate, live birth rate, and miscarriage rate were 63.0% vs. 30.8%, 51.9% vs. 7.7%, and 17.7% vs. 75% in the non-chronic and chronic endometritis groups, respectively. This criterion resulted in the highest pregnancy and live birth rates among the non-chronic endometritis and the smallest P values for the pregnancy rates, live birth rates, and miscarriage rates between the non-chronic and chronic endometritis groups. In the logistic regression analysis, chronic endometritis was an explanatory variable negatively affecting the objective variable of live birth only when chronic endometritis was diagnosed with ≥ 1 or ≥ 2 plasma cells per 10 high-power fields. The optimal cut-off value was obtained when one or more plasma cells were found in 10 high-power fields (sensitivity 87.5%, specificity 64.9%). Conclusions Chronic endometritis should be diagnosed as the presence of ≥ 1 plasma cells in 10 high-power fields. According to this diagnostic criterion, chronic endometritis adversely affected the pregnancy rate and the live birth rate.
Chlorin e6, loaded on the surface of SPION-PG-Lys8 through electrostatic attraction, was delivered preferentially into mitochondria of SKOV3 ovarian cancer cells, improving efficacy of photodynamic therapy significantly.
We report on application of pristine graphene as a drug carrier for phototherapy (PT).The loading of photosensitizer, chlorin e6 (Ce6), was achieved simply by sonication of Ce6 and graphite in aqueous solution. During the loading process, graphite was gradually exfoliated to graphene to give its composite with Ce6 (G-Ce6). This one-step approach is considered to be superior to the graphene oxide (GO) based composites, which required pretreatment of graphite by strong oxidation. Additionally, the directly exfoliated graphene ensured high drug loading capacity, 160 wt%, which is about ten times larger than that of the functionalized GO. Furthermore, the Ce6 concentration for killing cells by G-Ce6 is 6 -75 times less than that of the other Ce6 composites including GO-Ce6.Medicinal applications of nanomaterials, so-called "nanomedicine", have been attracting growing interest in recent years. Among various shapes of nanomaterials including nanotube and nanorod (1D), 1-3 nanosheet and layered one (2D), 4-6 and nanosphere and nanoparticle (3D), 7-9 a 2D-layered nanosheet, most typically a few layer graphene (FLG), has their own characteristics as a drug carrier; the flat structure, hydrophobic surface, and large specific surface area. 10,11 Although they are advantageous to load the anticancer drugs having flat structure and hydrophobic nature, the hydrophobicity prevents the carrier like FLG from dispersing in a physiological environment. To solve this problem, the graphenes have been strongly oxidized to generate numerous hydrophilic oxygen-containing functional groups and employed as drug carriers. 5,10,12,13 Obviously, this chemical modification of graphenes leading to graphene oxides (GOs) harms the planarity and hydrophobicity of the pristine graphenes, significantly decreasing the drug loading capacity and eventually losing the appeal of graphenes and 2D nanosheets as drug carriers.On the other hand, phototherapy (PT) including photodynamic therapy (PDT) and photothermal therapy (PTT) 3, 6, 14-16 is a promising noninvasive treatment for cancer. To increase the efficacy of the therapy, the photosensitizer should be delivered to the lesion as selectively as possible, most likely with aid of a carrier. It would be better if the loading capacity of the carrier is higher, as long as the composite has enough dispersibility in a physiological environment.Herein, we report, for the first time, on facile and convenient approach to fabricate the graphene-based composite with high drug-loading efficiency and enough aqueous dispersibility directly from pristine graphite and a photosensitizer (chlorin e6, Ce6). The composite was well dispersed in cell culture medium and directly applied to the cancer cell for PT. As a result, significant cytotoxicity was observed upon irradiation of light, while Ce6 without the graphene carrier was not cytotoxic irrespective of light irradiation. Ce6 is found to work not only as a photosensitizer in PT, but also an exfoliant and a dispersant for graphene. In addition, graphene in the composi...
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