Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules.

Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

Identification and verification of a ten-gene signature predicting overall survival for ovarian cancer.

BACKGROUND: This study was aimed to identify an accurate gene expression signature to predict overall survival (OS) in patients with ovarian cancer (OC). METHODS: Expression data and corresponding clinical information were obtained from two independent databases: the Cancer Genome Atlas (TCGA) dataset and International Cancer Genome Consortium (ICGC) dataset. Multiple analysis methods including univariate and multivariate COX regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis were utilized to build the signature. Receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analyses were used to assess the predictive accuracy of this gene signature. RESULTS: A novel 10-gene signature with high predictive accuracy for OS in OC patients was constructed and validated in the training and validation set. Based on the results of univariate and multivariate analyses, the presence of risk Score was identified as an independent prognostic factor for survival of OC patients. Moreover, we developed a nomogram model based on these 10 genes in the signature, which also displayed a favorable predictive efficacy for prognosis in OC. CONCLUSIONS: Our results identified a robust 10-gene signature for OC prognosis prediction, which might be applied to assist clinical decision-making and individualized treatment.

Self-assembled micelles based on gambogenic acid-phospholipid complex for sustained-release drug delivery.

Objective: To improve the water solubility and enhance the oral bioavailability of gambogenic acid (GNA). Methods: GNA-phospholipid complex (GNA-PLC) micelles were successfully prepared by anti-solvent method. Results: The encapsulation efficiency of GNA-PLC micelles can reach 99.33 % (w/w). The average particle size of the GNA-PLC micelles was 291.23 nm which was approximate agreed with the transmission electron microscopy (TEM). In vitro release profile showed the GNA-PLC and GNA-PLC micelles have significant sustained-release of GNA compared with crude GNA. Pharmacokinetic parameters indicated that the area under concentration-time curve (AUC0→t) of GNA in cases of GNA-PLC and GNA-PLC micelles are 2.04- and 3.92-fold higher than crude GNA, respectively. Conclusions: The better water solubility and higher bioavailability of GNA in GNA-PLC micelles with significant sustained-release of GNA endow the nanoparticle with great potential in GNA delivery system.

Eye exercises for myopia prevention and control: a comprehensive systematic review and meta-analysis of controlled trials.

OBJECTIVES: To evaluate the efficacy of eye exercises in preventing and controlling myopia. METHODS: We searched studies on eye exercises from nine Chinese and English databases from their inception to December 15, 2022. Using random-effect models and sensitivity/subgroup analyses, we estimated the effects of eye exercises compared to control on changes in three measures: visual acuity, refractive error (both quantified using standardized mean differences, SMDs), and protective/mitigating effects (assessed through risk ratios, RRs). RESULTS: Eleven studies were included in the meta-analysis, with 921 participants. Nine studies had some concerns of bias in at least two domains, and two studies had a high risk of bias in two domains. Seven studies used visual acuity to measure myopia; visual acuity declined after eye-exercise interventions (SMD = -0.67, 95% CI -1.28 to -0.07, Z = 2.17, P = 0.03) and the effect was not better than control (SMD = -0.50, 95% CI -1.16 to 0.16, Z = 1.49, P = 0.14). Two studies used refractive error to measure myopia; the effect of eye-exercise interventions did not differ from control (SMD = -1.74, 95% CI -6.27 to 2.79, Z = 0.75, P = 0.45). Seven studies reported on protective/mitigating effects; eye exercises exhibited a greater protective/mitigating effect than control (RR = 0.40, 95% CI 0.23-0.71, Z = 3.13, P < 0.01). CONCLUSIONS: Overall, the results suggest that eye exercises have limited to no efficacy in preventing or controlling myopia progression. Until robust evidence supports their efficacy, available evidence suggests retiring the eye-exercise policy.

Effects of machine perfusion strategies on different donor types in liver transplantation: a systematic review and meta-analysis.

BACKGROUND: The increasing use of extended criteria donors (ECD) sets higher requirements for graft preservation. Machine perfusion (MP) improves orthotopic liver transplantation (OLT) outcomes, but its effects on different donor types remains unclear. The authors' aim was to assess the effects of hypothermic machine perfusion (HMP), normothermic machine perfusion (NMP), or normothermic regional perfusion (NRP) versus static cold storage (SCS) on different donor types. MATERIALS AND METHODS: A literature search comparing the efficacy of MP versus SCS in PubMed, Cochrane, and EMBASE database was conducted. A meta-analysis was performed to obtain pooled effects of MP on ECD, donation after circulatory death (DCD), and donor after brainstem death. RESULTS: Thirty nine studies were included (nine randomized controlled trials and 30 cohort studies). Compared with SCS, HMP significantly reduced the risk of non-anastomotic biliary stricture (NAS) [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.26-0.72], major complications (OR 0.55, 95% CI 0.39-0.78), and early allograft dysfunction (EAD) (OR 0.46, 95% CI 0.32-0.65) and improved 1-year graft survival (OR 2.36, 95% CI 1.55-3.62) in ECD-OLT. HMP also reduced primary non-function (PNF) (OR 0.40, 95% CI 0.18-0.92) and acute rejection (OR 0.62, 95% CI 0.40-0.97). NMP only reduced major complications in ECD-OLT (OR 0.56, 95% CI 0.34-0.94), without favorable effects on other complications and survival. NRP lowered the overall risk of NAS (OR 0.27, 95% CI 0.11-0.68), PNF (OR 0.43, 95% CI 0.22-0.85), and EAD (OR 0.58, 95% CI 0.42-0.80) and meanwhile improved 1-year graft survival (OR 2.40, 95% CI 1.65-3.49) in control DCD-OLT. CONCLUSIONS: HMP might currently be considered for marginal livers as it comprehensively improves ECD-OLT outcomes. NMP assists some outcomes in ECD-OLT, but more evidence regarding NMP-ECD is warranted. NRP significantly improves DCD-OLT outcomes and is recommended where longer non-touch periods exist.

Expression of WW domain-containing oxidoreductase and its clinical implication in endometrial adenocarcinoma patients with metabolic syndrome.

AIM: Metabolic syndrome (MS) is tightly associated with the oncogenesis and prognosis of endometrioid adenocarcinoma, but the underlying mechanism is unclear. Here, we studied the relation between the expression status of WW domain-containing oxidoreductase (WWOX) and the clinicopathological features of endometrioid adenocarcinoma patients with MS. METHODS: Fifty-seven samples of endometrial adenocarcinoma were chosen for detection of expression level of WWOX. Overall survival (OS) time of these patients was analyzed by univariate and multivariate analysis. Survival analysis of patients with different WWOX expression levels from the Cancer Genome Atlas (TCGA) database was also performed. RESULTS: The WWOX expression is significantly higher in MS group than that in non-MS group (36.4% vs 65.7%, P = .03). WWOX was closely related to MS (P = .03) and muscle invasion of tumor cells (P = .04), but age, tumor grade, status of lymphatic metastasis, and FIGO (International Federation of Gynecology and Obstetrics) stage were not significantly different between the two WWOX expression status. Univariate analysis revealed that lymphatic metastasis (P = .023) and lower stage (P = .006) are significantly associated with OS. Multivariate analysis demonstrated that stage was an independent prognostic factor for OS (hazard ratio = 0.197; 95% CI, 0.043-0.896). Downregulation of WWOX was statistically associated with OS in patients from TCGA database (P = .04). CONCLUSION: WWOX may play an important role in the progression of endometrial cancer with MS.

The Correlation between the Determination of Vaginal Micro-Ecological Composition and the Outcome of HPV Infection by High-Throughput Metagene Sequencing Information Technology on the Illumina Platform.

OBJECTIVE: To study the correlation between vaginal micro-ecological composition and the outcome of human papillomavirus (HPV) infection by High-Throughput Metagene Sequencing Information Technology on the Illumina Platform, and to improve the efficiency of clinical infection detection. METHODS: With the aid of Illumina high-throughput sequencing platform and sequence research method, the composition and diversity of vaginal microorganisms in high-risk HPV (HR-HPV) infected women and healthy women were analyzed. The differences in vaginal flora of HR-HPV infected women and healthy women were compared to explore the correlation between HR-HPV infection and vaginal flora. RESULTS: The structure of vaginal flora in healthy women was relatively single, with Lactobacillus as the dominant genus, accounting for more than 80%. The structure of vaginal flora in women infected with HR-HPV was significantly different from that in non-infected women. The former had a significantly increased species diversity, which was mainly manifested by a decrease in Lactobacillus and an increase in Gardnerella vaginalis. Mycoplasma and Ureaplasma urealyticum might play a synergistic role in the initial stage of cervical lesions caused by HR-HPV infection. CONCLUSION: The prevention and treatment of mycoplasma and Ureaplasma urealyticum should be valued clinically to prevent the occurrence of HR-HPV infection and cervical lesions.

Preparation, physicochemical characterization and pharmacokinetics of paeoniflorin-phospholipid complex.

In order to enhance lipophilicity and oral bioavailability of paeoniflorin (PF), this study developed paeoniflorin-phospholipid complex (PF-PLC) by solvent-evaporation method. The optimum preparation technology of PF-PLC was screened by the combination of single factor and orthogonal experiment. The physicochemical properties of PF-PLC were evaluated via differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and oil-water partition coefficient study (lgP). The result of FTIR spectra indicated that there was some strong hydrogen bond interaction and good compatibility between the phospholipid molecule and PF in the complex. DSC and XRD structure analysis showed that PF was in form of amorphous structure in PF-PLC, and lgP of PF-PLC was enhanced, suggesting that the lipophilicity of PF-PLC was higher than that of PF. In vitro release of PF-PLC showed slower release than PF solution with its cumulative release rate of 93.81% at 24 h compared to 93.43% of PF at 1.5 h. In pharmacokinetic experiments, the AUC and Cmax of the PF-PLC were 1.97-fold and 2.5-fold higher than PF solution. These results suggested that PF-PLC could enhance lipophilicity and oral bioavailability of PF and provide a promising delivery system for the application of PF.

Preparation and preliminary pharmacokinetics study of GNA-loaded zein nanoparticles.

OBJECTIVES: Gambogenic acid (GNA), one of the main active ingredients isolated from Garcinia cambogia, has shown diverse antitumour activities. However, short biological half-life and low oral bioavailability severely limit its clinical application. Here, we developed GNA-loaded zein nanoparticles (GNA-ZN-NPs) based on phospholipid complex and zein nanoparticles to prolong the circulation time and enhance oral bioavailability of GNA. METHODS: The physicochemical properties of GNA-ZN-NP were characterized in details. The in vitro release profile, in vivo pharmacokinetic experiments and tissue distribution of GNA-ZN-NPs were also evaluated. KEY FINDINGS: The particle size, PDI and encapsulation efficiency of GNA-ZN-NPs were 102.90 nm, 0.027 and 76.35 ± 0.64%, respectively. The results of SEM, FTIR, DSC and XRD demonstrated that GNA-ZN-NPs were prepared successfully. The in vitro dissolution of GNA-ZN-NPs exhibited controlled release compared with raw GNA solution. The pharmacokinetic study showed that the AUC of GNA-ZN-NPs was significantly increased, and the t1/2 and MRT values of GNA-ZN-NPs were 3.21-fold and 2.19-fold higher than that of GNA solution. Tissue distribution results illustrated that GNA-ZN-NPs showed hepatic-targeting properties. CONCLUSION: GNA-ZN-NPs significantly enhanced the oral bioavailability and prolonged half-life of GNA, providing a promising oral drug delivery system to improve in vivo pharmacokinetic behaviour of GNA.

Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement.

OBJECTIVES: We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur. METHODS: Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated. KEY FINDINGS: Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution. CONCLUSIONS: The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application.