SPC25 Functions as a Prognostic-Related Biomarker, and Its High Expression Correlates with Tumor Immune Infiltration and UCEC Progression.

BACKGROUND: Most tumor tissues expressed spindle pole body component 25 (SPC25), one of the four subunits of the NDC80 complex, at greater levels compared to surrounding normal tissues. According to earlier researches, this subunit strongly encouraged tumor cell proliferation and tumor growth, which resulted in worse prognoses in patients with hepatocellular, breast, lung, and prostate cancer. Precisely because SPC25's role in uterine corpus endometrial carcinoma (UCEC) is understudied, we chose to concentrate on UCEC for gaining a more scientific and thorough understanding of SPC25. METHODS: Along with examining SPC25's differential expression, prognostic significance, and biological function in UCEC, our research sought to clarify the underlying mechanism by which SPC25 influences the course of UCEC and patient prognosis from the viewpoints of methylation and immune infiltration. RESULTS: We observed differential expression of SPC25 gene in different clinicopathological features of UCEC and identified SPC25 as a hazard factor for poorer overall survival (OS), disease-specific survival (DSS), and progress free interval (PFI) in UCEC, particularly in its multiple clinical subtypes. In addition, we also discovered that SPC25 and its co-expressed genes mostly engaged in biological processes and signal transduction routes linked to cell cycle and cell division in UCEC. After investigating SPC25's methylation status, we discovered that patients with UCEC had elevated SPC25 expression and a poor prognosis due to hypomethylation of CpG sites in the SPC25 gene sequence. Finally, we investigated SPC25's potential role in immunotherapy and discovered that SPC25 might alter the major immune cell infiltration levels in the tumor microenvironment (TME) by regulating the expression of immunoregulatory molecules and chemokines, which would be beneficial for SPC25 to control the progression of UCEC. CONCLUSIONS: In conclusion, SPC25 was a useful predictive biomarker as well as a possible therapeutic target for UCEC.

Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

Correlation of several forms of folic acid with endometrial cancer: cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2011-2018.

OBJECTIVE: Endometrial cancer (EC) is a common malignancy of the female reproductive system and although most patients have a good prognosis, 20-30% of patients with advanced disease have a poor prognosis. There are currently no reliable biomarkers for early diagnosis and effective prognostic improvement of the disease. The purpose of this study was to explore the correlation between different forms of folic acid and endometrial cancer. METHODS: This study included 8809 female subjects aged ≥ 20 years in the NHANES database from 2011 to 2018, including 8738 non-oncology patients and 71 EC patients. Selection bias was reduced using 1:1 propensity score matching (PSM) method. Restricted cubic spline (RCS) was plotted to explore the non-linear relationship between different forms of folic acid and EC. RESULT: Using data from the NHANES database from 2011 to 2018, the association between folic acid and the risk of developing EC was assessed. The results of the 1:1 ratio propensity score matching (PSM) showed 68 each for EC patients and non-oncology participants. Total serum folate, 5-methyltetrahydrofolate (5-methylTHF), 5-formyltetrahydrofolate (5-formylTHF), tetrahydrofolate (THF) and 5,10-methylenetetrahydrofolate (5,10-methenylTHF) were significantly correlated with EC (p < 0.05). In addition, the RCS showed a significant non-linear correlation between THF and 5,10-formyl THF and the risk of developing EC. CONCLUSION: The results of this study showed that changes in serum total folate, 5-methylTHF, 5-formylTHF, THF and 5,10-methenylTHF were related to EC.

MKRN2 inhibits the proliferation of gastric cancer by downregulating PKM2.

Cumulative evidence suggests that dysfunction of ubiquitinating enzymes is responsible for multiple types of diseases including cancer. However, what role the ubiquitinating enzyme plays in gastric cancer remains unknown. In this study, using bioinformatics analysis and a series of experimental analyses, we found that an E3 ubiquitin-protein, MKRN2 was down-regulated in gastric cancer tissues. Kaplan-Meier survival analysis showed the low MKRN2 expression significantly indicated poor prognosis. Overexpression of MKRN2 notably inhibited cell proliferation in vitro and in vivo. Conversely, knockdown of MKRN2 had the opposite effects in vitro. Additionally, the mechanical analysis indicated that MKRN2 promoted ubiquitination-mediated degradation of PKM2 and attenuated its effect on ERK. Overall, the present study suggests that MKRN2 may be a potential therapeutic target for gastric cancer.

Analysis of prognostic factors of metastatic endometrial cancer based on surveillance, epidemiology, and end results database.

Objective: To explore the risk factors for survival and prognosis of patients with metastatic endometrial cancer and to build and verify a reliable prediction model. Methods: We retrospectively analyzed patients diagnosed with metastatic endometrial cancer in the US Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Univariate and multivariate Cox regression analyses were used to assess clinical variables impact on survival and to construct nomograms. The results of the consistency index (C-index), subject operating characteristic (ROC) curve, and calibration curve were used to evaluate the predictive ability of the nomogram. Results: This study included 3,878 patients with metastatic endometrial cancer. In the univariate analysis, variables associated with overall survival (OS) and cancer-specific survival (CSS) included age, race, marital status, pathological type, pathological grade, T-stage, N-stage, surgery, radiotherapy, chemotherapy, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. In the multivariate analysis, age, race, pathological type, pathological grade, T-stage, N-stage, surgery, radiotherapy, chemotherapy, brain metastasis, liver metastasis, and lung metastasis were independent risk factors for OS and CSS (all P < 0.05). Combined with the results of the multiple factors, the 1-, 3-, 5-, and 8-year nomograms were constructed. For OS and CSS, T-stage had the greatest impact on the adverse prognosis of patients with metastatic endometrial cancer. The C-indexes of the OS and CSS nomograms in the training cohort were 0.749 (95% CI, 0.739-0.760) and 0.746 (95% CI, 0.736-0.756), respectively. The C-indices of OS and CSS in the validation cohort were 0.730 (95% CI, 0.714-0.746) and 0.728 (95% CI, 0.712-0.744), respectively. The ROC curve revealed our model's good prediction accuracy and clinical practicability. The calibration curve also confirmed the consistency between the model and actual existence. The Kaplan-Meier curves revealed statistically significant differences between the risk subgroups (P < 0.05). Conclusion: Our SEER-based nomograms for predicting survival in patients with metastatic endometrial cancer were helpful for the clinical evaluation of patient prognosis.

Clinical characteristics of female patients diagnosed with congenital adrenal hyperplasia and plastic-esthetic related thoughts: a retrospective study.

OBJECTIVES: Congenital adrenal hyperplasia (CAH) is a rare disorder that can cause masculinization of the external genitalia in females, usually evident in neonates. To present a case series of female patients with CAH by summarizing their clinical features and outcomes. DESIGN: This retrospective study analyzed the clinical data of female patients with CAH admitted to the First Affiliated Hospital of Xiamen University from 1995 to 2019. MATERIALS AND METHODS: Clinical characteristics, CAH subtype, treatments, and outcomes were summarized from the medical records and analyzed. Follow-up was conducted after drug therapy and surgical treatment and was censored in 2019. RESULTS: Twenty-one female patients were diagnosed with CAH: 21-hydroxylase deficiency (21-OHD) in 17 patients and 17α-hydroxylase deficiency (17α-OHD) in four patients. The clinical manifestations of 21-OHD were clitoral hypertrophy, pigmentation, male secondary sexual development, genital malformation, sexual precocity, nausea, and vomiting. The clinical manifestations of 17α-OHD were hypertension, feminization, sexual infantilism, and pigmentation. The patients received hormone replacement therapy. When necessary, some patients underwent external genital organ orthomorphia or artificial periodic therapy. Twelve patients were followed up; their sexual development was improved, but seven patients had poor breast development due to late diagnosis and/or poor hormone treatment adherence. CONCLUSION: Female CAH patients are subject to genital deformities, virilizing signs, breast dysplasia, and other appearance defects. The purpose of this report is to improve plastic and esthetic surgeons' understanding of CAH.

Intraoral Prosthetic Chin Augmentation With Vertical Incisions.

To explore a new surgical approach for chin augmentation using a prosthesis with 3 intraoral vertical incisions whereby placement of the prosthesis is more convenient and accurate, with fewer postoperative complications. Following the anatomic characteristics of the chin, a bilateral mucosal vertical incision and a median observation incision are made. The V-shaped mark on the upper side of the prosthesis can be seen through the observation incision after it is placed from the lateral incision into the predesigned compartment. The incision can be sutured if there is no bleeding in the operation area. Surgery performed in all 19 patients with mild microgenia with 6 to 12 months of follow-up resulted in satisfactory chin and face shape without any complications. The application of this novel method can correct McCarthy type I microgenia with more accurate positioning, less possibility of bilateral sideways and/or up/down movement, and fewer complications.

An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3ß/ß-Catenin Signaling Pathways.

Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3ß were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents.

Changes in the Zygomaticomaxillary Suture During Aging.

Trans-sutural distraction osteogenesis (TSDO) has been successfully used to correct midfacial hypoplasia in growing patients for years. The effects of TSDO, however, remain difficult to predict in adult patients. The aim of this study was to determine the biologic basis for the age-related increase in difficulty of performing TSDO. A total of 45 male Sprague Dawley (SD) rats were obtained in 3 age groups: 4 weeks old (4W, N = 15), 3 months old (3M, N = 15), and 13 months old (13M, N = 15). The zygomaticomaxillary sutures (ZMS) were dissected, and their morphology was evaluated by histology and micro-computed tomography (micro-CT). Quantitative real-time polymerase chain reaction of the ZMS and blood samples taken from the abdominal aorta were also used to assess the effects of age at the molecular level. Compared with the 4W rats, the number of fibroblasts in the ZMS was decreased, the bone plate adjacent to the ZMS was thicker, and the texture was denser in the 13M rats. Micro-computed tomography analysis showed the density of the ZMS was significantly increased in the 13M group (P < 0.05). The density ratio of the ZMS to the adjacent bone was increased from 0.14:1 in the 4M group to 0.54:1 in the 13M group. The gene expression of osteocalcin (OC) was significantly lower at 13M than at 3M (P < 0.05). The OC and alkaline phosphatase (ALP) serum levels were significantly lower at 13M than at 4W (P < 0.05). During aging, the decreased osteogenesis activity both systemically and locally may be the biologic effect that limits the application of TSDO in older patients.