Hydrophobic Cross-Linked Chains Regulate High Wet Tissue Adhesion Hydrogel with Toughness, Anti-hydration for Dynamic Tissue Repair.

Hydrogel adhesion materials are widely reported for tissue engineering repair applications, however, wet tissue surface moisture can reduce the wet-adhesion properties and mechanical strength of hydrogels limiting their application. Here, anti-hydration gelatin-acrylic acid-ethylene dimethacrylate (GAE) hydrogels with hydrophobic cross-linked chains are constructed. The prepared GAE hydrogel is soaked in PBS (3 days) with a volume change of 0.6 times of the original and the adhesive strength, Young's modulus, toughness, and burst pressure are maintained by ≈70% of the original. A simple and universal method is used to introduce hydrophobic chains as cross-linking points to prepare hydrogels with anti-hydration, toughness, and high wet state adhesion. The hydrophobic cross-linked chains not only restrict the movement of molecular chains but also hinder the intrusion of water molecules. Antihydration GAE hydrogels exhibit good biocompatibility, slow drug release, and dynamic oral wet-state tissue repair properties. Therefore, the anti-hydration hydrogel has excellent toughness, wet tissue adhesion properties, and good prospects for biological applications.

CD147: an integral and potential molecule to abrogate hallmarks of cancer.

CD147 also known as EMMPRIN, basigin, and HAb18G, is a single-chain type I transmembrane protein shown to be overexpressed in aggressive human cancers of CNS, head and neck, breasts, lungs, gastrointestinal, genitourinary, skin, hematological, and musculoskeletal. In these malignancies, the molecule is integral to the diverse but complimentary hallmarks of cancer: it is pivotal in cancerous proliferative signaling, growth propagation, cellular survival, replicative immortality, angiogenesis, metabolic reprogramming, immune evasion, invasion, and metastasis. CD147 also has regulatory functions in cancer-enabling characteristics such as DNA damage response (DDR) and immune evasion. These neoplastic functions of CD147 are executed through numerous and sometimes overlapping molecular pathways: it transduces signals from upstream molecules or ligands such as cyclophilin A (CyPA), CD98, and S100A9; activates a repertoire of downstream molecules and pathways including matrix metalloproteinases (MMPs)-2,3,9, hypoxia-inducible factors (HIF)-1/2α, PI3K/Akt/mTOR/HIF-1α, and ATM/ATR/p53; and also functions as an indispensable chaperone or regulator to monocarboxylate, fatty acid, and amino acid transporters. Interestingly, induced loss of functions to CD147 prevents and reverses the acquired hallmarks of cancer in neoplastic diseases. Silencing of Cd147 also alleviates known resistance to chemoradiotherapy exhibited by malignant tumors like carcinomas of the breast, lung, pancreas, liver, gastric, colon, ovary, cervix, prostate, urinary bladder, glioblastoma, and melanoma. Targeting CD147 antigen in chimeric and induced-chimeric antigen T cell or antibody therapies is also shown to be safer and more effective. Moreover, incorporating anti-CD147 monoclonal antibodies in chemoradiotherapy, oncolytic viral therapy, and oncolytic virus-based-gene therapies increases effectiveness and reduces on and off-target toxicity. This study advocates the expedition and expansion by further exploiting the evidence acquired from the experimental studies that modulate CD147 functions in hallmarks of cancer and cancer-enabling features and strive to translate them into clinical practice to alleviate the emergency and propagation of cancer, as well as the associated clinical and social consequences.

Field test of quantum key distribution over aerial fiber based on simple and stable modulation.

We have developed a simple time-bin phase encoding quantum key distribution system, using the optical injection locking technique. This setup incorporates both the merits of simplicity and stability in encoding, and immunity to channel disturbance. We have demonstrated the field implementation of quantum key distribution over long-distance deployed aerial fiber automatically. During the 70-day field test, we achieved approximately a 1.0 kbps secure key rate with stable performance. Our work takes an important step toward widespread implementation of QKD systems in diverse and complex real-life scenarios.

Surface roughness and gloss alteration of polished resin composites with various filler types after simulated toothbrush abrasion.

Background/purpose: Few studies have focused on the influence of simulated toothbrush abrasion on the surface qualities of novel nanofilled and nanohybrid composites. The aim of the study was to evaluate the surface roughness and gloss values of resin-based composite (RBC) materials with various filler types before and after simulated toothbrush abrasion. Materials and methods: One nanofilled (Filtek Z350 XT [FT3]), two nanohybrids (Harmonize [HM] and Clearfil Majesty [CM]) and one microhybrid (Filtek Z250 [FT2]) were evaluated. Twelve specimens of each material were made and polished with silicon carbide sandpapers. Initial surface roughness and gloss values were measured as negative controls. Then, all specimens were subjected to simulated toothbrush abrasion on a custom-made apparatus. After 2000, 4000 and 8000 cycles, the surface roughness and gloss values of all specimens were tested. One additional specimen from each group was selected for scanning electron microscope (SEM) analysis. Results: For FT3, Ra and GU values did not significantly change until after 8000 cycles during the process of toothbrushing (P > 0.05). For HM, CM and FT2, the Ra and GU values significantly decreased after 4000 and 8000 cycles of toothbrush abrasion (P < 0.05). After 8000 cycles of toothbrush abrasion, FT3 presented the lowest surface roughness and highest gloss values of all materials (P < 0.05). SEM images showed that surface textures and irregularities corresponded to the results of surface roughness and gloss. Conclusion: Surface roughness and gloss after simulated toothbrush abrasion were material dependent. Nanofilled resin composite presented the lowest Ra values and highest GU values.

Electrospun polycaprolactone incorporated with fluorapatite nanoparticles composite scaffolds enhance healing of experimental calvarial defect on rats.

Background: Composite scaffolds that maximize the advantages of different polymers are widely utilized in guided tissue regeneration (GTR). Some studies found that novel composite scaffolds composed of electrospun polycaprolactone/fluorapatite (ePCL/FA) actively promoted the osteogenic mineralization of various cell types in vitro. However, only a few studies have addressed the application of this composite scaffold membrane material in vivo. In this study, the ability of ePCL/FA composite scaffolds in vivo and their possible mechanisms were preliminarily explored. Methods: In this study, ePCL/FA composite scaffolds were characterized and their effects on bone tissue engineering and repair of calvarial defects in rats were examined. Sixteen male Sprague-Dawley (SD) rats were randomly categorized into four groups: normal group (integral cranial structure without defect), control group (cranial defect), ePCL group (cranial defect repaired by electrospun polycaprolactone scaffolds), and ePCL/FA group (cranial defect repaired by fluorapatite-modified electrospun polycaprolactone scaffolds). At 1 week, 2 months, and 4 months, micro-computed tomography (micro-CT) analysis was performed to compare the bone mineral density (BMD), bone volume (BV), tissue volume (TV), and bone volume percentage (BV/TV). The effects of bone tissue engineering and repair were observed by histological examination (hematoxylin and eosin, Van Gieson, and Masson respectively) at 4 months. Results: In water contact angle measurement, the average contact angle for the ePCL/FA group was significantly lower than that for the ePCL group, indicating that the FA crystal improved the hydrophilicity of the copolymer. Micro-CT analysis revealed that the cranial defect had no significant change at 1 week; however, the BMD, BV, and BV/TV of the ePCL/FA group were significantly higher than those of the control group at 2 and 4 months. Histological examination showed that the cranial defects were almost completely repaired by the ePCL/FA composite scaffolds at 4 months compared to the control and ePCL groups. Conclusions: The introduction of a biocompatible FA crystal improved the physical and biological properties of the ePCL/FA composite scaffolds; thus, these scaffolds demonstrate outstanding osteogenic potential for bone and orthopedic regenerative applications.

Beneficial effects of postoperative radiotherapy for IIIA­N2 non­small cell lung cancer after radical resection analysed using the propensity score­matching method.

The objective of the present study was to investigate the role of postoperative radiotherapy (PORT) after radical resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). Subgroups of patients who benefited from PORT were evaluated. A retrospective review of 288 consecutive patients with resected pIIIA-N2 NSCLC at Beijing Chest Hospital (Beijing, China) was performed. Of these patients, 61 received PORT. The 288 patients were divided into PORT and non-PORT groups according to the treatment received. The baseline characteristics of the two patient groups were balanced using propensity score-matching (PSM; 1:1 matching). In total, 60 patients in the PORT group and 60 patients in the non-PORT group were matched. After PSM, the median survival time of the matched patients was 53 months. The 1-, 3- and 5-year overall survival (OS) rates of the PORT patient group were 95.0, 63.2 and 48.2%, respectively, while those of the non-PORT group were 86.7, 58.3 and 34.5%, respectively, and there was no significant difference between the two groups (P=0.056). The 5-year local recurrence-free survival (LRFS) rate in the PORT group was significantly improved (P=0.001). The effects of PORT on OS and LRFS rates were analysed in patients with different clinicopathological features. For subgroups with multiple N2 stations, N2 positive lymph nodes ≥4 and squamous cell carcinoma, PORT significantly increased the OS and LRFS rates (P<0.05). In conclusion, there was no statistically significant improvement in the 5-year OS rate with PORT overall, but there may be subgroups, such as patients with multiple N2 stations, N2 positive nodes ≥4 and squamous cell carcinoma histology, that could be explored as potentially benefitting from improved 5-year OS and LRFS rates with PORT.

Effectiveness and cytotoxicity of two desensitizing agents: a dentin permeability measurement and dentin barrier testing in vitro study.

BACKGROUND: When evaluating the efficacy and safety of various desensitizing products in vitro, their mechanism of action and clinical utility should be considered during test model selection. This study aimed to evaluate the effects of two desensitizers, an in-office use material and an at-home use material, on dentin specimen permeability, and their dentin barrier cytotoxicity with appropriate test models. METHODS: Two materials, GLUMA desensitizer (GLU) containing glutaraldehyde and remineralizing and desensitizing gel (RD) containing sodium fluoride and fumed silica, were selected. Human dentin specimens were divided into three groups (n = 6): in groups 1 and 2, GLU was applied, and in group 3, RD was applied and immersed in artificial saliva (AS) for 24 h. Dentin specimen permeability before and after each treatment/post-treatment was measured using a hydraulic device under a pressure of 20 cm H2O. The perfusion fluid was deionized water, except in group 2 where 2% bovine serum albumin (BSA) was used. The representative specimens before and after treatment from each group were investigated using scanning electron microscopy. To measure cytotoxicity, test materials were applied to the occlusal surfaces of human dentin disks under which three-dimensional cell scaffolds were placed. After 24-h contact within the test device, cell viability was measured via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. RESULTS: GLU significantly reduced the dentin permeability and occluded the dentinal tubules when 2% BSA was used as perfusion fluid. RD significantly reduced dentin permeability and occluded the tubules, but permeability rebounded after AS immersion. GLU significantly decreased cell viability, but RD was non-cytotoxic. CONCLUSIONS: In vitro GLU application induced effective dentinal tubule occlusion only following the introduction of simulated dentinal fluid. RD provided effective tubule occlusion, but its full remineralization potential was not realized after a short period of immersion in AS. GLU may harm the pulp, whereas RD is sufficiently biocompatible.

Polymerization shrinkage and shrinkage stress of bulk-fill and non-bulk-fill resin-based composites.

Background/purpose: Bulk-fill resin-based composites (RBCs) are a new class of restorative materials, and polymerization shrinkage (PS) is concerned due to their single increment up to 4 mm. The aim of this study was to evaluate the PS and shrinkage stress (SS) of bulk-fill RBCs in vitro. Materials and methods: Three bulk-fill RBCs and three conventional non-bulk-fill RBCs were selected. The PS was determined with Acuvol volumetric shrinkage analyzer by calculating the specimen volume variation before and after light irradiation. The SS was investigated using universal testing machine method with a polymethyl methacrylate rod as a bonding substrate. The force generated during the polymerization process was detected by a load cell linked to a computer. SS was calculated by dividing the maximum stress force by the area of the rod. Results: The mean PS of various RBCs ranged from 1.72% to 2.13%. All PS results of bulk-fill RBCs were comparable to their conventional counterparts. Sonicfill 2 (SF2) and Harmonize (HM) showed the lowest PS (p < 0.05; Tukey HSD test). Medians of SS results ranged from 0.55 MPa to 0.67 MPa. All SSs of bulk-fill RBCs were comparable to their conventional counterparts. SF2 showed significantly lower SS than Tetric N-Ceram (TN) and Tetric N-Ceram Bulk Fill (TNB) (p < 0.0083; post hoc comparisons with Bonferroni adjustments). A moderate, positive correlation was observed between PS and SS with Pearson's correlation (r = 0.446, p = 0.013). Conclusion: Both PS and SS are material dependent. A moderate, positive correlation between PS and SS is found with new bulk-fill RBCs and their conventional counterparts.

Janus mucosal dressing with a tough and adhesive hydrogel based on synergistic effects of gelatin, polydopamine, and nano-clay.

There are many problems and challenges related to the treatment of highly prevalent oral mucosal diseases and oral drug delivery because of a large amount of saliva present in the oral cavity, the accompanying oral movements, and unconscious swallowing in the mouth. Therefore, an ideal oral dressing should possess stable adhesion and superior tough strength in the oral cavity. However, this fundamental requirement greatly limits the use of synthetic adhesive dressings for oral dressings. Here, we developed a mussel-inspired Janus gelatin-polydopamine-nano-clay (GPC) hydrogel with controlled adhesion and toughness through the synergistic physical and chemical interaction of gelatin (Gel), nano-clay, and dopamine (DA). The hydrogel not only exhibits strong wet adhesion force (63 kPa) but also has high toughness (1026 ± 100 J m-3). Interfacial adhesion of hydrogels is achieved by modulating the interaction of catechol groups of the hydrogel with specific functional groups (e.g., NH2, SH, OH, and COOH) on the tissue surface. The matrix dissipation of the hydrogel is regulated by physical crosslinking of gelatin, chemical crosslinking of gelatin with polydopamine (Michael addition and Schiff base formation), and nano-clay-induced constraint of the molecular chain. In addition, the GPC hydrogel shows high cell affinity and favors cell adhesion and proliferation. The hydrogel's instant and strong mucoadhesive properties provide a long-lasting therapeutic effect of the drug, thereby enhancing the healing of oral ulcers. Therefore, mussel-inspired wet-adhesion Janus GPC hydrogels can be used as a platform for mucosal dressing and drug delivery systems. STATEMENT OF SIGNIFICANCE: It is a great challenge to treat oral mucosal diseases due to the large amount of saliva present in the oral cavity, the accompanying oral movements, unconscious swallowing, and flushing of drugs in the mouth. To overcome the significant limitations of clinical bioadhesives, such as weakness, toxicity, and poor usage, in the present study, we developed a simple method through the synergistic effects of gelatin, polydopamine, and nano-clay to prepare an optimal mucosal dressing (Janus GPC) that integrates Janus, adhesion, toughness, and drug release property. It fits effectively in the mouth, resists saliva flushing and oral movements, provides oral drug delivery, and reduces patient discomfort. The Janus GPC adhesive hydrogels have great commercial potential to support further the development of innovative therapies for oral mucosal diseases.

Epimedin C Alleviates Glucocorticoid-Induced Suppression of Osteogenic Differentiation by Modulating PI3K/AKT/RUNX2 Signaling Pathway.

Secondary osteoporosis is triggered mostly by glucocorticoid (GC) therapy. Dexamethasone (DEX) was reported to inhibit osteogenic differentiation in zebrafish larvae and MC3T3-E1 cells in prior research. In this research, we primarily examined the protective impacts of epimedin C on the osteogenic inhibition impact of MC3T3-E1 cells and zebrafish larvae mediated by DEX. The findings illustrated no apparent toxicity for MC3T3-E1 cells after administering epimedin C at increasing dosages from 1 to 60 µM and no remarkable proliferation in MC3T3-E1 cells treated using DEX. In MC3T3-E1 cells that had been treated using DEX, we discovered that epimedin C enhanced alkaline phosphatase activities and mineralization. Epimedin C could substantially enhance the protein expression of osterix (OSX), Runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALPL) in MC3T3-E1 cells subjected to DEX treatment. Additionally, epimedin C stimulated PI3K and AKT signaling pathways in MC3T3-E1 cells that had been treated using DEX. Furthermore, in a zebrafish larvae model, epimedin C was shown to enhance bone mineralization in DEX-mediated bone impairment. We also found that epimedin C enhanced ALPL activity and mineralization in MC3T3-E1 cells treated using DEX, which may be reversed by PI3K inhibitor (LY294002). LY294002 can also reverse the protective impact of epimedin C on DEX-mediated bone impairment in zebrafish larval. These findings suggested that epimedin C alleviated the suppressive impact of DEX on the osteogenesis of zebrafish larval and MC3T3-E1 cells via triggering the PI3K and AKT signaling pathways. Epimedin C has significant potential in the development of innovative drugs for the treatment of glucocorticoid-mediated osteoporosis.

The prognostic value of the preoperative inflammatory index on the survival of glioblastoma patients.

OBJECTIVES: The growth and development of tumors are closely related to the initiation and amplification of the inflammatory response. Various inflammatory biomarkers had attained growing attention for nearly two decades and were discovered strongly associated with cancer patients' prognosis, indicating that systemic inflammatory response is possibly essential to cancer progression. However, little was known about the sensitive biomarkers associated with the detection, persistence, treatment, and prognosis of GBM. Hence, the retrospective research endeavored to evaluate the prognostic value of preoperative inflammatory biomarkers in patients with GBM who initially received standardized treatment. METHODS: The 232 glioblastoma patients eligible who were admitted to Qilu Hospitals in Shandong Province from January 2014 to January 2018 were collected for this analysis. Inflammatory markers, including the systemic immune-inflammation index (SII), systemic immune response index (SIRI), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and albumin/globulin ratio (AGR), were designed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and we calculated the area under the ROC curve to determine the AUC value. Besides, we used the Cox proportional hazard model to estimate the relationship between variables and PFS and OS. The statistical differences between variables and PFS and OS were tested through the log-rank test. What is more, the LR method was used to perform Cox multiple regression analysis. The results were represented by hazard ratio (HR), 95% CI, any 2-tailed P < 0.01 was accepted as statistically different. RESULTS: The multivariate Cox proportional hazard model presented that SII ≥ 659.1 was an independent risk factor affecting OS (HR = 2.238, 95% CI = 1.471-3.406, P < 0.001) and postoperative PFS (HR = 2.000, 95% CI = 1.472-2.716, P < 0.001) in GBM patients. The 1-, 3-, and 5-year OS of the SII < 659.1 group was 70.8%, 26.9%, and 14.1%, respectively, while the 1- and 3-year OS of the SII ≥ 659.1 group was 37.5% and 11.5% (P < 0.001). The 1-, 3-, and 5-year PFS of the SII < 659.1 group was 36.3%, 19.6%, and 13%, respectively, while the 1-year PFS of the SII ≥ 659.1 group was 11.3% (P < 0.001). Results of patients' clinical and pathological characteristics paraded that in comparison to the lower SII group, the higher SII group had significantly inferior Karnofsky Performance Scale (KPS) scores (P < 0.001) and more frequent cystic changes of the tumors (P < 0.001), whereas the values of SIRI, NLR, PLR, MLR, and AGR were low. CONCLUSIONS: SII is an independent inflammatory indicator for predicting the prognosis of GBM patients after receiving initially standardized treatments.

Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration.

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects. However, typical resorbable membranes composed of collagen (Col) have insufficient mechanical properties and high degradation rate, while non-resorbable membranes need secondary surgery. Herein, we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium (Col/PCLMA/Mg) composite membrane that provided spatiotemporal support effect after photocrosslinking. Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed; Col membranes and PCL membranes were used as controls. After photocrosslinking, an interpenetrating polymer network was observed by scanning electron microscopy (SEM) in Col/PCL and Col/PCL/Mg membranes. The elastic modulus, swelling behavior, cytotoxicity, cell attachment, and cell proliferation of the membranes were evaluated. Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM. The membranes were implanted into calvarial bone defects of rats for 8 weeks. The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus (p < 0.05), and a lower swelling rate (p < 0.05), than Col membranes, and there were no differences in cell biocompatibility among groups (p > 0.05). The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes, both in vivo and in vitro (p < 0.05). The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8 (p < 0.05). The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential, which meets clinical needs.

Ultrasonic-Assisted Aqueous Two-Phase Extraction Combined with Macroporous Resin Enrichment of Lignans from Flaxseed Meal and Their Antioxidant Activities.

BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a natural antioxidant generally extracted from flaxseed, which is one of the most important oil crops in China, the by-product of the flaxseed oil, i.e., flaxseed meal still contains a lot of lignans. However, flaxseed meal is generally treated as waste, resulting in a huge waste of resources. OBJECTIVE: To establish an efficient and convenient method for extraction and purification of lignans from flaxseed meal. METHODS: First, we used response surface methodology (RSM) to optimize the extraction conditions of the ultrasonic-assisted (UA) aqueous two-phase system (ATPS), and we obtained the purified extracts by macroporous resin purification (MRP). Second, the antioxidant ability of the extracts was studied in vitro. RESULTS: The best extraction conditions obtained were as follows: 9.0% (w/w) sodium hydroxide; 30.0% (w/w) isopropanol; extraction time, 39 min; liquid-to-solid ratio, 52.0 mL/g; ultrasonic wave, 560 W; and extraction temperature, 40°C. Under the optimal conditions, the purity of crude extracts (SDG-APTS-C) reached 21.5%. The desorption conditions of MRP were as follows: eluting 3 BV with ultrapure water, and then eluting with 25% ethanol at 2 BV (bed volume)/h to collect eluents. The purified extracts (SDG-ATPS-P) had a purity quotient of 73.9%, which was 52.4% higher than that of SDG-ATPS-C. Additionally, experiments conducted revealed that SDG-ATPS-C and SDG-ATPS-P could effectively remove DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS （2,-Azinobis-3-ethylbenzthiazoline-6-sulphonate）, and hydroxyl free radicals in vitro. CONCLUSIONS: The method was validated for extracting SDG from flaxseed meal, thus achieving the reuse of flaxseed meal. HIGHLIGHTS: This research provides some references for the application of UAATPS combined with MRP in natural products.

Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan Charge-Reversal Nanocarriers for Triggered Drug Release.

Biodegradable nanoparticles and micelles are promising nanosystems for the targeted delivery of potent anticancer drugs. By using specialized polymers as nanocarriers, targeted drug delivery and release can be developed. We developed thiol-hyaluronic acid (HA-SH)/chitosan (CS) nanoparticles with redox/pH dual-responsiveness via electrostatic self-assembly followed by spontaneous chemical cross-linking. The nanoparticle surface charges were reversible through different HA-SH and CS mass ratios. Doxorubicin (DOX) was used as a model drug. Dual cross-linked nanoparticles with diameters of approximately 300 nm exhibited superior stability under physiological conditions compared with nanoparticles without disulfide cross-linking. DOX was loaded more efficiently into negative nanoparticles (45.7 wt%) than positive nanoparticles (14.2 wt%). Drug release from negative nanoparticles (ζ potential of approximately -20) was higher (87.8 wt%) at pH 4.5 and in the presence of 10 mM glutathione. Positive nanoparticles (ζ potential of approximately +20) showed the same trend, but the release rate was slower than that of negative nanoparticles. DOX-loaded HA-SH/CS particles were taken up by human breast cancer cells (SKBR3), and the loaded drug was released, exhibiting potential antitumor efficacy. The HA-SH/CS nanoparticles in this study were stable under physiological conditions and are promising candidates for the targeted delivery and release of anticancer drugs.

Clinical Efficacy and Safety of Human Mesenchymal Stem Cell Therapy for Degenerative Disc Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Degenerative disc disease (DDD) can cause severe low back pain, which will have a serious negative impact on the ability to perform daily tasks or activities. For the past few years, mesenchymal stem cell (MSC) transplantation has emerged as a promising strategy for the treatment of DDD. However, the clinical efficacy of MSC in the treatment of DDD still lacks clinical evidence and is controversial. We conducted a meta-analysis with randomized controlled trials (RCTs) to evaluate the clinical efficacy and safety of MSC transplantation in patients with DDD. We searched major databases using terms from the database's inception through March 2021. The Cochrane bias risk assessment tool was used to assess quality. The analysis showed that MSC therapy could decrease visual analog scale (VAS) scores (SMD = -0.50, 95%CI = -0.68 ~ -0.33, P < 0.00001) and Oswestry Disability Index (ODI) scores (SMD = -0.27, 95%CI = -0.44 ~ -0.09, P = 0.003). The outcomes with subgroup analysis showed that MSC therapy could decrease VAS scores in 3 months (P = 0.001), 6 months (P = 0.01), 12 months (P = 0.02), and ≥24 months (P = 0.002) and ODI scores in ≥24 months (P = 0.006). Pooled analysis showed that MSC therapy has a higher ratio of patients at most thresholds but particularly at the MIC (minimally important change) (P = 0.0002) and CSC (clinically significant change) (P = 0.0002) in VAS and MIC (P = 0.0005) and CSC (P = 0.001) pain responders in ODI. Adverse events (AE) of treatment-emergent adverse events (TEAE), back pain, arthralgia, and muscle spasms were not statistically significant between the two groups. However, our further statistical analysis showed that MSC therapy may induce AE of TEAE related to study treatment (OR = 3.05, 95%CI = 1.11 ~ 8.40, P = 0.03). In conclusion, this study pooled the main outcomes and showed that MSC therapy could significantly decrease VAS and ODI scores in patients with DDD. Distinctly, the findings of this meta-analysis suggest a novel therapeutic strategy for patients with chronic low back pain (LBP) and lumbar dysfunction by DDD.

The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment.

Diabetes mellitus and osteoporosis are closely related and have complex influencing factors. The impact of anti-diabetic drugs on bone metabolism has received more and more attention. Type 2 diabetes mellitus (T2DM) would lead to bone fragility, high risk of fracture, poor bone repair and other bone-related diseases. Furthermore, hypoglycemic drugs used to treat T2DM may have notable detrimental effects on bones. Thus, the clinically therapeutic strategy for T2DM should not only effectively control the patient's glucose levels, but also minimize the complications of bone metabolism diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel and promising drug for the treatment of T2DM. Some studies have found that GLP-1RAs may play an anti-osteoporotic effect by controlling blood sugar levels, promoting bone formation and inhibiting bone resorption. However, in clinical practice, the specific effects of GLP-1RA on fracture risk and osteoporosis have not been clearly defined and evidenced. This review summarizes the current research findings by which GLP-1RAs treatment of diabetic osteoporosis, postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and describes possible mechanisms, such as GLP-1R/MAPK signaling pathway, GLP-1R/PI3K/AKT signaling pathway and Wnt/ß-catenin pathway, that are associated with GLP-1RAs and osteoporosis. The specific role and related mechanisms of GLP-1RAs in the bone metabolism of patients with different types of osteoporosis need to be further explored and clarified.

2,5-Dimethyl Celecoxib Inhibits Proliferation and Cell Cycle and Induces Apoptosis in Glioblastoma by Suppressing CIP2A/PP2A/Akt Signaling Axis.

2,5-Dimethyl-celecoxib (DMC) is a close structural analog of the selective COX-2 inhibitor celecoxib that lacks COX-2-inhibitory function. Thus, DMC is a promising drug for anti-tumor. In this study, we evaluated the efficacy and the molecular basis of DMC in the treatment of human glioblastoma multiforme (GBM). DMC inhibited the growth and proliferation of GBM cell lines (LN229, A172, U251, and U87MG) in a dose-dependent manner (P < 0.001). In GBM cells treated with DMC, detection by flow cytometry showed cell cycle arrest, and proteins involved in cell cycle such as P21 were increased. Compared with control group, Annexin-V/PI-staining in DMC-treatment group was increased, indicating that DMC could induce apoptosis in GBM cells. Also, associated proteins including cleaved caspase 3 and cleaved PARP-1 were increased. It was further explored whether DMC blocked cell cycle and induced apoptosis in GBM cells through CIP2A/PP2A/AKT signaling pathway. After treatment of DMC, the phosphorylation of Akt was reduced while the total Akt level was not affected. DMC suppressed the expression of CIP2A in a time-dependent manner, while the CIP2A overexpression group reversed cell cycle and apoptotic protein expression led by DMC. Finally, in a xenograft model in nude mice using LN229 cells, DMC suppressed tumor growth. These findings proved that DMC could block cell cycle and induce apoptosis in GBM cells by suppressing CIP2A/PP2A/Akt signaling axis, which indicated that DMC could be an effective option for GBM treatment.

Fabrication and Application of a 3D-Printed Poly-ε-Caprolactone Cage Scaffold for Bone Tissue Engineering.

Poly-ε-caprolactone (PCL) is a promising synthetic material in bone tissue engineering (BTE). Particularly, the introduction of rapid prototyping (RP) represents the possibility of manufacturing PCL scaffolds with customized appearances and structures. Bio-Oss is a natural bone mineral matrix with significant osteogenic effects; however, it has limitations in being constructed and maintained into specific shapes and sites. In this study, we used RP and fabricated a hollow-structured cage-shaped PCL scaffold loaded with Bio-Oss to form a hybrid scaffold for BTE. Moreover, we adopted NaOH surface treatment to improve PCL hydrophilicity and enhance cell adhesion. The results showed that the NaOH-treated hybrid scaffold could enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMMSCs) both in vitro and in vivo. Altogether, we reveal a novel hybrid scaffold that not only possesses osteoinductive function to promote bone formation but can also be fabricated into specific forms. This scaffold design may have great application potential in bone tissue engineering.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: a preferential benefit for squamous cell carcinoma.

BACKGROUND: The beneficial effect of postoperative radiotherapy (PORT) on completely resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of the study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC. PATIENTS AND METHODS: Between October 2010 and September 2016, 288 consecutive patients with completely resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed, which consisted of 194 cases of LADC and 85 cases of LSCC. There were 42 (21.6%) patients treated with PORT in LADC cases and 19 (22.3%) patients treated with PORT in LSCC cases. The 5-year overall survival (OS), loco-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The prognostic factors were determined using Cox's regression model. RESULTS: Among 194 cases of LADC, the 1-, 3-, and 5-year OS in the PORT group were 95.2%, 61.9% and 40.0%, respectively, while in the non-PORT group were 90.1%, 63.3% and 45.0% (p = 0.948). The use of postoperative chemotherapy (POCT) and smoking index ≥ 400 were both prognostic factors of 5-year rates of OS, LRFS and DMFS. On the other hand, among 85 cases of LSCC, the 1-, 3-, and 5-year OS in the PORT group were 94.7%, 63.2% and 63.2%, respectively, whereas in the non-PORT group were 86.4%, 48.5% and 37.1% (p = 0.026). In this group, only the use of PORT was a favorable prognostic factor for 5-year OS, LRFS and DMFS. CONCLUSIONS: Due to clinicopathological differences among completely resected pIIIA-N2 NSCLC, PORT may not be suitable to all patients. Our study distinguishes pIIIA-N2 LSCC from LADC by their positive responses to PORT.

Religion Affiliation and Depression Risk: Factory Workers Working in Hi-Tech Companies in Shanghai, China.

This study examines factors contributing to depression among migrant factory workers in Shanghai. A survey was designed with mental health questions under a framework explaining: (1) social capital, (2) migratory stress, and (3) mental health consequences. With a return rate of 98.3%, 1966 individuals completed the survey. Only 11.1% of the respondents indicated having a religious affiliation. The findings are not surprising about the relationship between trust, economic condition, and depression. However, it is surprising to find that not having a religious affiliation is significantly connected to better mental health. The effect of religious beliefs should be examined as a trust factor to remove the barrier of perceiving religion as an added stressor.