Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Malignant glioma is the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo had been demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. Consistent with previous studies, a size and dose dependent antitumor effect and significant radiosensitivity enhancing effect of AgNPs were observed in our experiment system. We also found that cell protective autophagy could be induced by AgNPs and/or radiation, which was verified by the use of 3-MA. The mechanism through which had autophagy and the enhancement of radiosensitivity taken place was further investigated with inhibitors of ERK and JNK pathways. We demonstrated that ERK and JNK played pivotal roles in the radiosensitivity enhancement. Inhibiting ERK and JNK with U0126 and SP600125 respectively, we found that the autophagy level of the cells treated with AgNPs and radiation were attenuated. Moreover, SP600125 down-regulated the apoptosis rate of the co-treated cells significantly. Taken together, the present study would have important impact on biomedical applications of AgNPs and clinical treatment for glioma.     

Macroporous thin membranes for cell transplant in regenerative medicine

The aim of this paper is to present a method to produce macroporous thin membranes made of poly (ethyl acrylate-co-hydroxyethyl acrylate) copolymer network with varying cross-linking density for cell transplantation and prosthesis fabrication. The manufacture process is based on template techniques and anisotropic pore collapse. Pore collapse was produced by swelling the membrane in acetone and subsequently drying and changing the solvent by water to produce 100 microns thick porous membranes. These very thin membranes are porous enough to hold cells to be transplanted to the organism or to be colonized by ingrowth from neighboring tissues in the organism, and they present sufficient tearing stress to be sutured with surgical thread. The obtained pore morphology was observed by Scanning Electron Microscope, and confocal laser microscopy. Mechanical properties were characterized by stress–strain experiments in tension and tearing strength measurements. Morphology and mechanical properties were related to the different initial thickness of the scaffold and the cross-linking density of the polymer network. Seeding efficiency and proliferation of mesenchymal stem cells inside the pore structure were determined at 2 h, 1, 7, 14 and 21 days from seeding.     

National level data analysis of facial lacerations in Korea using the National Health Insurance Service (NHIS) database

No national epidemiological investigations have been conducted recently regarding facial lacerations. The study was performed using the data of 3,634,229 people during the 5-year period from 2014 to 2018 archived by the National Health Information Database (NHID) of the Health Insurance Review and Assessment Service. Preschool and children under 10 years old accounted for about one-third of patients. Facial lacerations were concentrated in the “T-shaped” area, which comprised forehead, nose, lips, and the perioral area. The male to female ratio for all study subjects was 2.16:1. Age and gender are significantly related with each other (P < .001). Mean hospital stays decreased, and numbers of outpatient department visits per patient were highest for hospitals and lowest for health agencies. Over the study period, hospital costs per patient in tertiary and general hospitals increased gradually. Preschool and school-aged children are vulnerable to trauma. Male patients outnumbered female patients by a factor of more than 2. The “T-shaped’” area around forehead is vulnerable to injury. Total cost of medical care benefits per patient in tertiary hospitals was about 7 times on average than in health agencies. Regarding functional, behavioral, and aesthetic outcomes, more attention should be paid to epidemiologic data and hospital costs for facial lacerations.     

Decline in skeletal muscle mass is associated with cognitive decline in type 2 diabetes mellitus

AimsTo examine the longitudinal association between skeletal muscle mass (SMM) loss and cognitive decline over time in type 2 diabetes mellitus (T2DM).MethodsWe conducted a prospective cohort study of 453 patients from SMART2D cohort with follow-up intervals of 1.6 to 6.4 years. Baseline and follow-up measurements included bio-impedance analysis (BIA) measure of skeletal muscle mass index (SMI) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measure of cognitive function. We examined the association between annual rate of SMI and RBANS scores using linear regression, adjusting for demographics, education, depression, clinical co-variables and presence of apolipoprotein E4 (APOE) _?4 allele.ResultsThe mean age of participants was 60.3 ± 7.4 years. Compared to patients with Tertile 1 SMI change, the group with greater SMI decline (Tertile 3 SMI change) experienced 0.30 decline in RBANS total score (95%CI ?0.57 to ?0.03; p = 0.030) in the adjusted analysis. RBANS scores for subdomains in immediate memory and visuo-spatial/construction were lower in Tertile 3 SMI change group with corresponding coefficients ?0.54 (95%CI ?1.01 to ?0.06; p = 0.026), and ?0.71 (95%CI ?1.30 to ?0.12; p = 0.019) respectively.ConclusionIn patients with T2DM, BIA measure of muscle mass loss over time was independently associated with cognitive decline globally and in the domains of memory and visuo-spatial/construction.     

LncRNA GAS5 upregulates Smad4 to suppress the apoptosis of chondrocytes induced by lipopolysaccharide

Background: Osteoarthritis (OA) is closely correlated with inflammation. It has been reported that lncRNA GAS5 plays an important role in inflammation, indicating the potential involvement of GAS5 in OA. This study was carried out to investigate the function of GAS5 in OA.Methods: Expression levels of GAS5 in synovial fluid from 45 OA patients and 45 healthy controls were measured by RT-qPCR. Cell transfections were performed to explore the potential interactions among GAS5, miR-146a, and Smad4 in chondrocytes. Lipopolysaccharide (LPS)-induced cell apoptosis after overexpression of GAS5, miR-146a, and Smad4 was analyzed by cell apoptosis assay.Results: GAS5 was downregulated in OA. Moreover, LPS treatment downregulated GAS5 in chondrocytes. Interaction between GAS5 could with miR-146a was predicted by bioinformatics analysis and further confirmed by RNA-RNA pulldown assay. However, overexpression of GAS5 and miR-146a did not affect the expression of each other. GAS5 overexpression increased Smad4 expression in chondrocytes. In contrast, miR-146a overexpression downregulated Smad4 in chondrocytes. Moreover, GAS5 and Smad4 overexpression inhibited LPS- induced chondrocytes apoptosis, while miR-146a overexpression played an opposite role and attenuated the effects of GAS5 and Smad4 overexpression on cell apoptosis.Conclusion: GAS5 might sponge miR-146a to upregulate Smad4, thereby suppressing LPS- induced chondrocytes apoptosis.     

The effects of increased forward trunk lean during stair ascent on hip adduction and internal rotation in asymptomatic females

BackgroundIncreased hip adduction and internal rotation can lead to excessive patellofemoral joint stress and contribute to patellofemoral pain development. The gluteus maximus acts as a hip extensor, abductor, and external rotator. Improving hip extensor use by increasing one’s forward trunk lean in the sagittal plane may improve frontal and transverse plane hip kinematics during stair ascent.Research questionDoes increasing forward trunk lean during stair ascent affect peak hip adduction and internal rotation?MethodsTwenty asymptomatic females performed five stair ascent trials (96 steps/min) on an instrumented stair using their self-selected and forward trunk lean postures. Three-dimensional kinematics (200 Hz) and kinetics (2000 Hz) were recorded during the stance phase of stair ascent. Biomechanical dependent variables were calculated during the stance phase of stair ascent and included peak forward trunk lean, hip flexion, hip adduction, hip internal rotation angles, and the average hip extensor moment.ResultsDuring the forward trunk lean condition, decreases were observed for peak hip adduction (MD = 2.8˚; 95% CI = 1.9, 3.8; p < 0.001) and peak hip internal rotation (MD = 1.1˚; 95% CI = 0.1, 2.2; p = 0.04). In contrast, increases were observed during the forward trunk lean condition for the peak forward trunk lean angle (MD = −34.7˚; 95% CI = −39.1, −30.3; p < 0.001), average hip extensor moment (MD = −0.5 N·m/kg; 95% CI = −0.5, −0.4; p < 0.001), and stance time duration (MD = −0.02 s; 95% CI = −0.04, 0.00; p = 0.017).SignificanceIncreasing forward trunk lean and hip extensor use during stair ascent decreased peak hip adduction and internal rotation in asymptomatic females. Future studies should examine the effects of increasing forward trunk lean on hip kinematics, self-reported pain, and function in individuals with patellofemoral pain.     

Combining CAPRA-S With Tumor IDC/C Features Improves the Prognostication of Biochemical Recurrence in Prostate Cancer Patients

Background: Intraductal carcinoma and cribriform (IDC/C) tumor features are well-established prognosticators of biochemical recurrence (BCR), metastasis, and prostate cancer (PCa)-specific mortality. However, approximately 70% of PCa patients undergoing a radical prostatectomy are IDC/C negative, yet up-to 20% of these patients progress and experience BCR. Thus, tumor histopathologic characteristics such as IDC/C alone are limited in their ability to predict disease progression. Conversely, several nomograms such as Cancer of the Prostate Risk Assessment-Surgery (CAPRA-S) have been developed to aid in the prognostication of BCR, but not yet widely applied in clinical settings. Materials and methods: In this study, we assessed the combined prognostic utility of IDC/C, and CAPRA-S for BCR in 3 PCa patient cohorts. Results: CAPRA-S+IDC/C improved the predictive accuracy of BCR in all 3 cohorts (P < .001). Specifically, among IDC/C negative cases, CAPRA-S improved the prognostication of BCR in low-risk (Cohort 1; P < .001, Cohort 2; P < .001, Cohort 3; P = .003), intermediate (Cohort 1; P < .001, Cohort 2; P = .006, Cohort 3; P = .03) and high-risk (Cohort 1-3; P < .001) patients. Conversely, IDC/C improved the prognostication of BCR among CAPRA-S low-risk (Cohorts 1; P < .001 and Cohort 3; P = .003) patients. Conclusion: Our results suggest the investigation of histopathological IDC/C features in CAPRA-S low-risk patients and conversely, nomogram CAPRA-S among IDC/C negative patients improves the identification of patients likely to experience BCR, which would otherwise be missed through current assessment regimens. These patients can be offered more intensive monitoring and adjuvant therapies upfront to circumvent the development of recurrent cancer or overtreatment at the time of surgery.     

Ultrasonographic Analyses of the Forehead Region for Injectable Treatments

Botulinum toxin type A (BoNT-A) injections in the forehead region should only target the frontalis. This study applied ultrasonography with the aim of providing guidelines for predicting the layered structure and soft-tissue thickness of the forehead. We performed ultrasound scanning at 7 facial landmarks in 40 Korean adults. Allowing for the error range, the minimum depth from the skin to exclude the muscle layer was 2.3 mm, and the maximum depth from the skin to include the muscle layer was 2.8 mm. Of the total 7 points from the skin to muscle surface, significant differences between the males and females were found in 6 points (p < 0.05). Clinicians can use ultrasonography to identify the structural layers of the scalp. Even if ultrasound-guided injections are not performed, it is possible to target only muscle layers in BoNT-A injections by maintaining a needle depth of around 2.5 mm.     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.