Visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors: A retrospective cohort study.

OBJECTIVE: To investigate the visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors (PitNETs). METHODS: A retrospective study was conducted on 28 patients who developed evident postoperative hematoma out of a total of 9,010 patients. The hematomas were classified into three types based on their CT appearance. Type 1a - mild high density with no tension, Type 1b - thin-layer high density; Type 2a - solid high density with large empty cavities, Type 2b - solid high density with small empty cavities; Type 3 -solid high density with no cavity showing high tension. Patient data were collected for analysis. RESULTS: The study cohort comprised 10 female and 18 male patients, with a mean age of 51.5±11.9 years. Most patients presented with large adenomas (median diameter 36mm). Postoperative visual sight improved in 12 patients, remained stable in 11 patients, and worsened in 5 patients. Notably, no patients experienced worsened visual sight beyond twenty-four hours after the operation. Among the five patients with visual deterioration, four had CT type 3 hematoma (4/6, 66.7%), and one had CT type 2b hematoma (1/9, 11.1%). Patients in the type 3 CT group were significantly more prone to experience visual deterioration compared to those in the type 2 group (odds ratio [OR] 2.154 [95% CI 1.858-611.014], P=.027). Four patients underwent repeat surgery after visual deterioration, resulting in visual improvement following a prolonged recovery period. Postoperative hematoma had limited impact on pituitary dysfunction and hyponatremia. CONCLUSION: Our study reveals a significant association between postoperative hematoma CT types and visual deterioration. For patients with stable visual sight and type 1 or 2a hematoma, conservative strategies may be considered. Conversely, type 2b and 3 patients are at higher risk of visual deterioration, especially within the first 24 hours after the operation. Consequently, early reoperation before vision worsens may be a prudent approach to reduce risks and improve visual outcomes, particularly in type 3 patients.

The characteristics of brain structural remodeling in patients with unilateral vestibular schwannoma.

PURPOSE: Brain structural remodeling alters related brain function. However, few studies have assessed morphological alterations of unilateral vestibular schwannoma (VS) patients. Therefore, this study examined the characteristics of brain structural remodeling in unilateral VS patients. METHODS: We recruited 39 patients with unilateral VS (19 left, 20 right) and 24 matched normal controls (NCs). We obtained brain structural imaging data using 3T T1-weighted anatomical and diffusion tensor imaging scans. Then, we evaluated both gray and white matter (WM) changes using FreeSurfer software and tract-based spatial statistics, respectively. Furthermore, we constructed a structural covariance network to assess brain structural network properties and the connectivity strength between brain regions. RESULTS: Compared with NCs, VS patients showed cortical thickening in non-auditory areas (e.g., the left precuneus), especially left VS patients, along with reduced cortical thickness in the right superior temporal gyrus (auditory areas). VS patients also showed increased fractional anisotropy in extensive non-auditory-related WM (e.g., the superior longitudinal fasciculus), especially right VS patients. Both left and right VS patients showed increased small-worldness (more efficient information transfer). Left VS patients had a single reduced-connectivity subnetwork in contralateral temporal regions (right-side auditory areas), but increased connectivity between some non-auditory regions (e.g., left precuneus and left temporal pole). CONCLUSION: VS patients exhibited greater morphological alterations in non-auditory than auditory areas, with structural reductions seen in related auditory areas and a compensatory increase in non-auditory areas. Left and right VS patients show differential patterns of brain structural remodeling. These findings provide a new perspective on the treatment and postoperative rehabilitation of VS.

Effects and mechanisms of natural products on Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in elderly people with a high incidence rate and complicated pathogenesis, and causes progressive cognitive deficit and memory impairment. Some natural products and bioactive compounds from natural sources show great potential in the prevention and treatment of AD, such as apple, blueberries, grapes, chili pepper, Monsonia angustifolia, cruciferous vegetables, Herba epimedii, Angelica tenuissima, Embelia ribes, sea cucumber, Cucumaria frondosa, green tea, Puer tea, Amanita caesarea and Inonotus obliquus, via reducing amyloid beta (Aß) deposition, decreasing Tau hyperphosphorylation, regulating cholinergic system, reducing oxidative stress, inhibiting apoptosis and ameliorating inflammation. This review mainly summarizes the effects of some natural products and their bioactive compounds on AD with the potential molecular mechanisms.

Novel patient-derived xenograft and cell line models for therapeutic screening in NF2-associated schwannoma.

Treatment of schwannomas in patients with neurofibromatosis type 2 (NF2) is extremely unsatisfactory, and innovative therapeutic approaches are urgently needed. However, the lack of clinically relevant NF2-associated schwannoma models has severely hampered drug discovery in this rare disease. Here we report the first establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which recapitulates the morphological and histopathological features of patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannomas. Using gene expression profiling, we identified elevated PI3K/AKT/mTOR networks in human NF2-associated vestibular schwannomas. Using high-throughput screening of 157 inhibitors targeting the PI3K/AKT/mTOR pathways in vitro, we identified a dozen inhibitors (such as BEZ235, LY2090314, and AZD8055) with significant growth-suppressive effects. Interestingly, we observed that three cell lines displayed differential therapeutic responses to PI3K/AKT/mTOR inhibitors. Furthermore, we demonstrated that two orally bioavailable inhibitors, AZD8055 and PQR309, suppressed NF2-associated schwannoma growth both in vitro and in vivo. In conclusion, our novel patient-derived models of NF2-associated schwannoma closely mimic the phenotypes and genotypes of patient tumors, making them reliable preclinical tools for testing novel personalized therapies. © 2022 The Pathological Society of Great Britain and Ireland.

Management principles of cranial base tumor with aneurysm.

Skull base tumors are challenging to treat because of their deep location, complex anatomy, and close proximity to important blood vessels and nerves. Furthermore, some patients with cranial tumors are found to have aneurysms, but there is no consensus on how to evaluate the impact of aneurysms on surgery and how to handle the lesions safely and effectively. We retrospectively reviewed our database to identify all patients with a skull base tumor treated in the Department of Neurosurgery of Beijing Tiantan Hospital affiliated with Capital Medical University from 2019 to 2021. The records of patients with skull base tumors associated with aneurysms were analyzed. The operative methods and postoperative follow-up information were collected. We analyzed a total of 481 patients with skull base tumors, comprising 224 males and 257 females with a mean age of 48 ± 14 years. Twenty-four patients (24/481, 5.0%) were diagnosed with aneurysms. For eight patients, it was considered necessary to perform aneurysm treatment before or during the tumor resection surgery. For the other 16 patients, the recommendation was to monitor the aneurysm or perform elective aneurysm treatment after tumor resection. All patients with both skull base tumors and aneurysms benefited from treatment. No severe postoperative complications occurred. We summarized the final treatment plan for all patients with skull base tumors with aneurysms and proposed a protocol to decrease the surgical risk of patients with skull base tumors associated with aneurysms.

Intraoperative cerebrospinal fluid leakage and residual tumors in endoscopic transsphenoidal surgery for pituitary adenoma: risk analysis and nomogram development.

BACKGROUND: Endoscopic transsphenoidal surgery is the primary method used to treat pituitary adenomas (PAs) at present; however, this technique is associated with certain risks, including cerebrospinal fluid leakage (CFL) and residual tumors (RTs). In this study, we aimed to identify specific risk factors for intraoperative CFL (ioCFL) and postoperative RT in patients with pituitary adenoma and construct a corresponding nomogram for risk assessment. METHODS: We collected a range of information from 782 patients who underwent endoscopic transsphenoidal PA resection in the Department of Neurosurgery at Beijing Tiantan Hospital between 2019 and 2021. Patients were then randomly assigned to training and validation groups (in a 8:2 ratio) with R software. Univariate and multivariable logistic regression models were then used to screen variables related to ioCFL and RT. These variables were then used to construct a predictive nomogram. Finally, the accuracy of the nomogram was validated by receiver operating characteristic curve (ROC) analysis, calibration plots, and decision curve analysis (DCA). RESULTS: Univariate and multivariable logistic regression models identified four risk factors for ioCFL (Hardy grade, tumor size, position, and consistency) and five risk factors for RT (operation time, tumor size, consistency, Knosp grade, and primary/recurrence type). The area under the ROC curve (AUC) for the ioCFL risk model was 0.666 and 0.697 for the training and validation groups, respectively. For RT, the AUCs for the two groups were 0.788 and 0.754, respectively. The calibration plots for the ioCFL and RT models showed high calibration quality and DCA analysis yielded excellent efficiency with regards to clinical decision making. CONCLUSION: Tumor size, growth characteristics, and invasion location were identified as the main factors affecting intraoperative CFL and RT. With our novel nomogram, surgeons can identify high-risk patients according to preoperative and intraoperative tumor performance and reduce the probability of complications.

Operative management of trigeminal schwannomas: based on a modified classification in a study of 93 cases.

BACKGROUND: Advances in microscopic and endoscopic surgical techniques have outpaced traditional classification and transcranial surgical strategies, especially with reference to the treatment of trigeminal schwannomas (TSs). A modified TS classification is proposed and appropriate surgical strategies are discussed. METHODS: The cases of 93 patients who underwent surgical treatment in Beijing Tiantan Hospital in the previous 6 years were analyzed retrospectively, and a literature review was conducted. RESULTS: Classification is based on surgical direction. Tumors were classified as follows: type A, backward orientation, located in the orbit or orbit and middle cranial fossa (8 cases, 8.6%); type B, upward orientation, located in the pterygopalatine fossa, infratemporal fossa or pterygopalatine fossa, infratemporal fossa, and middle cranial fossa (23 cases, 24.7%); type C, forward and backward orientations, located in the middle cranial fossa, posterior cranial fossa or both (58 cases, 62.4%); and type D, located in multiple regions (4 cases, 4.3%). 91.40% of patients underwent gross total resection (GTR) with 29 cases receiving endoscopic resection of whom 93.10% (27/29) experienced GTR. CONCLUSION: The 93 cases were satisfactorily divided into four types, according to tumor location and surgical orientation, enabling safe and effective removal by appropriate surgery.

Patellar Tendon-Trochlear Groove Angle Measured on a Single Computed Tomography Slice of the Distal Femoral Trochlear Groove Is a Reliable Measurement for the Evaluation of Patellar Instability.

PURPOSE: To verify the reliability of patellar tendon-trochlear groove angle (PTTG-A) measured by computed tomography (CT) and the clinical significance in evaluation of patellar instability. METHODS: A retrospective study of hospitalized patients with knee pain or injury and had knee CT from January 2017 to June 2021 was performed. PTTG-A and tibial tuberosity-trochlear groove (TT-TG) distance were measured on CT. Spearman correlation analysis was analyzed between the 2 measurements. The intraclass correlation coefficient was determined for inter- and intraobserver reproducibility. The capacity of PTTG-A and TT-TG to predict patellar instability was evaluated by the receiver operating characteristic curve. Data from the control group were used to determine the pathologic thresholds and logistic regression analysis. RESULTS: Included were 113 patients. There were 60 patients with the history of at least 2 episodes of patellar dislocation (study group) and 53 patients without a history of patellar dislocation (control group). The respective PTTG-A and TT-TG distances in the study group (35.2 ± 8.4° and 19.6 ± 4.6 mm) were significantly greater than those of the controls (20.8 ± 5.8° and 13.3 ± 4.5 mm) (P < .001). The correlation between the 2 measurements was strong (r = 0.730, P < .001). The inter- and intraobserver reliability of the PTTG-A were better than TT-TG distance in both groups. The AUC of PTTG-A was greater than that of the TT-TG distance (0.895 vs 0.769, respectively). With the cutoff value of PTTG-A and TT-TG being 26.3° and 16.3 mm, the value of the pathologic threshold of PTTG-A was 30.0°, with a dominance ratio of 16.88 (95% confidence interval 2.88-98.89, P = .002). CONCLUSIONS: The PTTG-A measured on a single CT slice of the distal femoral trochlear groove is a more reliable measurement than TT-TG distance for the prediction of patellar instability. LEVEL OF EVIDENCE: III; A retrospective cohort study.

Posterior fossa ependymoma with preoperative cerebrospinal metastases: a case report with literature review.

BACKGROUND: Adult posterior fossa ependymomas (PF-EPN) with preoperative cerebrospinal metastases are extremely rare. Only 3 cases have been reported in previous literature. CASE PRESENTATION: A case of a 32-year-old male patient complained of headaches for three months. Pure tone audiometry showed a slight decrease in bilateral hearing. Auditory evoked potential indicated that the hearing on the left was slightly weaker than that on the right. Magnetic resonance imaging (MRI) revealed a primary tumor arising within the fourth ventricle and metastasizing to bilateral cerebellopontine angle (CPA), the third ventricle, the left lateral ventricle, T1, L1-2 and L5. A gross total resection (GTR) was performed on the lesion located in the left CPA. The histological examination showed a papillary ependymoma (WHO grade II). Immunohistochemical staining for H3K27me3 showed that nuclear positivity in more than 80% of cells. No NF2 mutation was observed. No progression was found during a 24-month follow-up. CONCLUSIONS: Our data indicate that preoperative multiple metastases in adult PF-EPN are extremely rare. This kind of disease usually has a low WHO grade and a favorable prognosis. GTR should be achieved when feasible and patients need a long-term follow-up with MRI.

Quantitative Detection of Tank Floor Defects by Pseudo-Color Imaging of Three-Dimensional Magnetic Flux Leakage Signals.

Highly integrated three-dimensional magnetic sensors have just been developed and have been used in some fields, such as angle measurement of moving objects. The sensor used in this paper is a three-dimensional magnetic sensor with three Hall probes highly integrated inside; 15 sensors are used to design the sensor array and then measure the magnetic field leakage of the steel plate; the three-dimensional component characteristics of the magnetic field leakage are used to determine the defect area. Pseudo-color imaging is the most widely used in the imaging field. In this paper, color imaging is used to process magnetic field data. Compared with analyzing the three-dimensional magnetic field information obtained directly, this paper converts the magnetic field information into color image information through pseudo-color imaging and then obtains the color moment characteristic values of the color image in the defect area. Moreover, the least-square support-vector machine and particle swarm optimization (PSO-LSSVM) algorithm are used to quantitatively identify the defects. The results show that the three-dimensional component of the magnetic field leakage can effectively determine the area range of defects, and it is feasible to use the color image characteristic value of the three-dimensional magnetic field leakage signal to identify defects quantitatively. Compared with a single component, the three-dimensional component can effectively improve the identification rate of defects.

CircRNA AFF4 induced by KDM1A promotes osteogenic differentiation through FNDC5/Irisin pathway.

BACKGROUND: Circular RNA (circ) AFF4 was documented to regulate osteogenesis but the underlying mechanism remains to be elucidated. The preliminary study showed that circ_AFF4 may promote osteogenesis via FNDC5/Irisin. Furthermore, the online prediction tool indicated the interaction of circ_AFF4, insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), FNDC5 and lysine (K)-specific demethylase 1 A (KDM1A). Therefore, this study aims to elucidate the relationships of KDM1A, circ_AFF4, IGF2BP3 and FNDC5/Irisin during osteogenesis. METHODS: The alkaline phosphatase (ALP) activities and osteogenic-related factors were determined using ALP and alizarin red S (ARS) staining, real-time quantitative PCR(RT-qPCR) and western blot. Immunoprecipitation (RIP), pull-down assay and fluorescence in situ hybridization (FISH) were used to examine the interactions among circ_AFF4/IGF2BP3/FNDC5. A mouse in vivo model was utilized to further confirm the regulatory effect on bone formation. RESULTS: Circ_AFF4 and KDM1A expression levels were increased during osteoinduction of BM-MSCs. Knockdown of circ_AFF4 and KDM1A significantly suppressed BM-MSC osteogenesis. We also proved that KDM1A directly bound to circ_AFF4 and FNDC5 promoter and induced circ_AFF4 and FNDC5 expression. Furthermore, circ_AFF4 enhanced the stability of FNDC5 by generating a circ_AFF4, IGF2BP3 and FNDC5 RNA-protein complex, and thereby induced Irisin and osteogenesis. The in vitro data was confirmed with in vivo model. CONCLUSION: These findings elucidate that KDM1A induces circ_AFF4, which promotes promote osteogenesis via IGF2BP3. This study indicates that circ_AFF4 may potentially represent a critical therapeutic target for the diseases.

Efficient side-chain deacylation of polymyxin B1 in recombinant Streptomyces strains.

OBJECTIVES: Polymyxins are antibacterial polypeptides used as "last resort" therapy option for multidrug-resistant Gram-negative bacteria. The expansion of polymyxin-resistant infections has inspired development of novel polymyxin derivatives, and deacylation is one of the critical steps in generating those antibiotics. Deacylase from Actinoplanes utahensis hydrolyze the acyl moieties of echinocandins, and also efficiently deacylates daptomycin, ramoplanin and other important antibiotics. Here, deacylase was studied considering its potential usefulness in deacylating polymyxin B1. RESULTS: All the six recombinant strains containing the deacylase gene catalyzed hydrolysis of polymyxin B1, yielding cyclic heptapeptides. The efficiency of recombinant S. albus (SAL701) was higher than that of the others, and deacylation was the most efficient at 40 °C in 0.2 M Tris buffer (pH 8.0) with 0.2 M Mg2+. The optimal substrate concentration of SAL701 was increased from 2.0 to 6.0 g/L. SAL701 was highly thermostable, showing no loss of activity at 50 °C for 12 h, and the mycelia could be recycled at least three times without loss of catalytic activity. SAL701 could not deacylate ß-lactam substrate such as penicillin G and cephalosporin C. Deacylase catalyzes the amide bond 1 closest to the nucleus of polymyxin B1 rather than the other bond, suggesting that it has high catalytic site specificity. Homology modeling and the docking results implied that Thr190 in deacylase could facilitate hydrolysis with high regioselectivity. CONCLUSIONS: These results show that SAL701 is effective in increasing the cyclic heptapeptide moiety of polymyxin B1. These properties of the biocatalyst may enable its development in the industrial production of polymyxins antibiotics.

miR-185-5p Represses Cells Growth and Metastasis of Osteosarcoma via Targeting Cathepsin E.

Osteosarcoma (OS) is a malignant bone tumor characterized by poor prognosis due to its regional invasion and early metastasis. In this study, we aimed to find the role and the underlying mechanism of Cathepsin E (CTSE) in OS growth and metastasis. We found CTSE is upregulated in metastatic OS, rather than in the primary lesion, as confirmed by RT-qPCR and western blot analysis of clinical OS samples. Furthermore, both in vitro and in vivo experiments illustrated that CTSE promoted both growth and metastasis of OS cells, partially mediated through the modulation of Epithelial-Mesenchymal Transition (EMT). Bioinformatics analysis predicted that miR-185-5p downregulates CTSE via directly binding to the 3'UTR of CTSE, which was verified by luciferase reporter assay and rescue assays. This study reported for the first time that CTSE is a potential biomarker in OS tumorigenesis and metastasis, providing a promising therapeutic target for OS treatment.

Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review.

Cancer has been a serious public health problem. Berberine is a famous natural compound from medicinal herbs and shows many bioactivities, such as antioxidant, anti-inflammatory, antidiabetic, anti-obesity, and antimicrobial activities. In addition, berberine shows anticancer effects on a variety of cancers, such as breast, lung, gastric, liver, colorectal, ovarian, cervical, and prostate cancers. The underlying mechanisms of action include inhibiting cancer cell proliferation, suppressing metastasis, inducing apoptosis, activating autophagy, regulating gut microbiota, and improving the effects of anticancer drugs. This paper summarizes effectiveness and mechanisms of berberine on different cancers and highlights the mechanisms of action. In addition, the nanotechnologies to improve bioavailability of berberine are included. Moreover, the side effects of berberine are also discussed. This paper is helpful for the prevention and treatment of cancers using berberine.

Rank-driven salp swarm algorithm with orthogonal opposition-based learning for global optimization.

Salp swarm algorithm (SSA) is a relatively new and straightforward swarm-based meta-heuristic optimization algorithm, which is inspired by the flocking behavior of salps when foraging and navigating in oceans. Although SSA is very competitive, it suffers from some limitations including unbalanced exploration and exploitation operation, slow convergence. Therefore, this study presents an improved version of SSA, called OOSSA, to enhance the comprehensive performance of the basic method. In preference, a new opposition-based learning strategy based on optical lens imaging principle is proposed, and combined with the orthogonal experimental design, an orthogonal lens opposition-based learning technique is designed to help the population jump out of a local optimum. Next, the scheme of adaptively adjusting the number of leaders is embraced to boost the global exploration capability and improve the convergence speed. Also, a dynamic learning strategy is applied to the canonical methodology to improve the exploitation capability. To confirm the efficacy of the proposed OOSSA, this paper uses 26 standard mathematical optimization functions with various features to test the method. Alongside, the performance of the proposed methodology is validated by Wilcoxon signed-rank and Friedman statistical tests. Additionally, three well-known engineering optimization problems and unknown parameters extraction issue of photovoltaic model are applied to check the ability of the OOSA algorithm to obtain solutions to intractable real-world problems. The experimental results reveal that the developed OOSSA is significantly superior to the standard SSA, currently popular SSA-based algorithms, and other state-of-the-artmeta-heuristic algorithms for solving numerical optimization, real-world engineering optimization, and photovoltaic model parameter extraction problems. Finally, an OOSSA-based path planning approach is developed for creating the shortest obstacle-free route for autonomous mobile robots. Our introduced method is compared with several successful swarm-based metaheuristic techniques in five maps, and the comparative results indicate that the suggested approach can generate the shortest collision-free trajectory as compared to other peers.

Continuous dural suturing for closure of grade 3 leaks after tumor removal via an endoscopic endonasal approach.

Cerebrospinal fluid (CSF) leakage is a major complication after extended endonasal transsphenoidal surgery (EETSS), which is commonly used in the treatment of anterior skull base tumors. Dural suturing and graded reconstruction are promising techniques to further decrease the incidence of postoperative CSF (poCSF) leakage. The effect of continuous dural suturing in endoscopic surgery was investigated in this retrospective study. A total of 79 EETSS patients were included; the procedures were performed for subdural tumor removal by a single endoscopic neurosurgical team. Comparisons were applied between patients who did and did not undergo endoscopic dural suturing after tumor removal. Multivariate logistic regression analysis was performed to identify variables that significantly influenced the incidence of poCSF leakage. In all, 79 adult patients developed Esposito's grade 3 intraoperative high-flow CSF leakage. Ten patients (12.7%) experienced poCSF leakage. One of the 36 patients who underwent intraoperative dural suturing developed poCSF leakage, compared with nine of 43 patients who did not undergo dural suturing (p = 0.016). Regression analysis showed that dural suturing could significantly decrease the incidence of poCSF leakage (p = 0.049, OR 0.108, 95% CI 0.013-0.899). Prophylactic lumbar drainage could also help decrease the CSF leakage rate. Dural suturing under endoscopy is a promising and effective method for application in skull base reconstruction after subdural skull base tumor removal. With future progress, lumbar drainage and even nasoseptal flap placement could be replaced in certain groups of patients undergoing EETSS.

Deceleration capacity of heart rate predicts trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer: A prospective observational study.

WHAT IS KNOWN AND OBJECTIVES: Trastuzumab is the standard choice for anti-human epidermal growth factor receptor 2 (HER2) therapy. Cardiotoxicity is one of the main adverse effects of trastuzumab. How to early predict trastuzumab-related cardiotoxicity remains a significant problem in clinical practice. The deceleration capacity of the heart rate (DC) has been shown to be a powerful predictor of adverse outcomes in various heart diseases. In the study, the role of DC in early predicting trastuzumab-related cardiotoxicity was investigated. METHODS: A total of 150 patients were prospectively investigated the clinical value of the DC in predicting trastuzumab-related cardiotoxicity in patients with HER2-positive breast cancer treated with trastuzumab at Guangxi Medical University Cancer Hospital from June 2015 to June 2017. DC, mean heart rate and heart rate variability (HRV) indices, including the standard deviation of all normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD), were assessed before treatment, and the left ventricular ejection fraction (LVEF) was regularly monitored for 2 years (before, during and after treatment) to evaluate cardiotoxicity. RESULTS: Among 150 eligible patients, 28 (18.7%) developed cardiotoxicity. Patients with cardiotoxicity were older (P < .05), higher anthracycline dose (P < .001) and had lower RMSSD (P < .05), SDNN, DC and baseline LVEF (P < .001), than patients without cardiotoxicity. Logistic regression analysis revealed lower DC, lower baseline LVEF and higher anthracycline dose were independent risk factors of trastuzumab-related cardiotoxicity. Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for DC than for the baseline LVEF in predicting cardiotoxicity (0.88 vs 0.77, P = .032). Additionally, DC had higher sensitivity (78.6% vs 67.9%) and specificity (83.6% vs 77.9%) in predicting cardiotoxicity than the baseline LVEF. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset (P < .01). WHAT IS NEW AND CONCLUSION: The present study found that DC was a stronger predictor of trastuzumab-related cardiotoxicity development than the baseline LVEF and HRV. Linear regression analysis showed among patients who developed cardiotoxicity, lower DC was associated with an earlier onset. DC should be a potential clinical indicator for the early prediction of trastuzumab-related cardiotoxicity.

Factors Affecting Extracellular Vesicles Based Drug Delivery Systems.

Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS.

Eriodictyol and naringenin inhibit the formation of AGEs: An in vitro and molecular interaction study.

Maillard reaction occurs between the carbonyl group of reducing sugars and the free amino groups of protein, which eventually results in the formation and accumulation of advanced glycation end products (AGEs) irreversibly. Excessive production of AGEs is associated with many diseases, such as Alzheimer disease, neuropathy, retinopathy, and nephropathy. In this study, the effects of eriodictyol and naringenin on the inhibition of AGEs were studied with bovine serum albumin (BSA)-methylglyoxal (MGO) model by spectroscopic techniques and molecular docking methods. The fluorescence spectroscopy results suggested that eriodictyol and naringenin could inhibit the formation of AGEs. Circular dichroism (CD) studies indicated that eriodictyol and naringenin could stabilize the structure of BSA and inhibit the formation of AGEs. The molecular docking results demonstrated that eriodictyol formed two hydrogen bonds with Lys 350 and Leu 480 and the main forces were hydrogen bonding and hydrophobic interactions. However, naringenin interacted with Arg 484 of BSA, and the main force was hydrophobic interaction. It can be concluded that eriodictyol and naringenin can inhibit the formation of AGEs and eriodictyol has stronger inhibitory activity of AGEs than that of naringenin, which is probably due to the additional hydroxyl group in the position C-3' of B ring of eriodictyol.

Three-dimensional bio-printed constructs consisting of human umbilical-derived mesenchymal stem cells promote cell viability, proliferation, and differentiation in vitro.

The aim of this study was to investigate the effect of three-dimensional (3D) bio-printed constructs consisting of human umbilical-derived mesenchymal stem cells (HUMSCs) on cell viability, proliferation and differentiation in vitro. Functional 3D bio-printed microspheres consisting of HUMSCs were constructed using electrostatic inkjet technique. The parameters used for the synthesis of 3D bio-printed tissue constructs were first optimized. The viability, proliferation and differentiation of 3D cultured HUMSCs were assessed. The results of scanning electron microscopy (SEM) showed that isolated HUMSCs exhibited fibroblast-like spindle adherent growth. The optimized printing parameters were 6 kV voltage, 10 mL/h flow, 15 cm receiving height, and alginate: water ratio of 1:1 mixed at 37 °C. Compared with 2D cultured HUMSCs, the 3D cultured HUMSCs have better viability, proliferation and differentiation ability. The results obtained in this study indicate that 3D bio-printed tissue constructs promote HUMSC viability, proliferation, and neural differentiation in vitro.