Parental willingness to accept and pay human papillomavirus vaccine for boys aged 9-14 in a metropolis area of China: Evidence for developing a vaccination strategy.

BACKGROUND: Increasing countries are expanding the human papillomavirus (HPV) vaccination to men, which has not yet been licensed in China. This study investigated the parental willingness to accept (WTA) and pay (WTP) HPV vaccine for their sons aged 9-14. METHODS: In Shanghai, a metropolis area of China, parents with boys aged 9-14 were recruited to complete an online questionnaire using a convenience sampling strategy. Parental WTA were determined for parents themselves and for their sons. Parental preference of HPV vaccine was measured using discrete choice experiment in two assumed government subsidy scenarios that referred to HPV vaccination subsidy mechanisms for girls in China. Additionally, parental WTP was estimated using contingent valuation method. RESULTS: A total of 2493 parents with boys aged 9-14 were included in the study. Majority of mothers (88.99 % and 90.99 %) and fathers (79.57 % and 85.04 %) showed WTA HPV vaccine for themselves and sons, respectively. Parental gender, age, monthly household income, knowledge, and awareness were positively associated with parental WTA for their sons (each P < 0.05). Remarkably, more mothers showed specific preference of HPV vaccine for themselves (53.67 %) and sons (47.78 %), while more fathers showed no preference for themselves (46.76 %) and sons (53.81 %). In the two assumed government subsidy scenarios, parents mostly preferred domestic HPV vaccines for themselves and sons (each P < 0.05). Additionally, mothers had significantly higher WTP for sons (mean value, 2122.75 CNY) than fathers did (1695.40 CNY) (P < 0.001). However, parental WTP was similar between for themselves and for sons, regardless of mothers and fathers (each P > 0.05). CONCLUSION: Parents have high WTA and WTP HPV vaccine for boys aged 9-14 in Shanghai, which may provide evidence for preparing HPV vaccination strategy. Acceptance of HPV vaccines and roll-out in boys could be enhanced through the availability of government subsidy mechanism and domestic HPV vaccines.

Photoresponsive metal-organic framework with combined photodynamic therapy and hypoxia-activated chemotherapy for the targeted treatment of rheumatoid arthritis.

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.

Stearic acid promotes lipid synthesis through CD36/Fyn/FAK/mTORC1 axis in bovine mammary epithelial cells.

Stearic acid (C18:0, SA) is a saturated long-chain fatty acid (LCFA) that has a prominent function in lactating dairy cows. It is obtained primarily from the diet and is stored in the form of triacylglycerol (TAG) molecules. The transmembrane glycoprotein cluster of differentiation 36 (CD36) is also known as fatty acid translocase, but whether SA promotes lipid synthesis through CD36 and FAK/mTORC1 signaling is unknown. In this study, we examined the function and mechanism of CD36-mediated SA-induced lipid synthesis in bovine mammary epithelial cells (BMECs). SA-enriched supplements enhanced lipid synthesis and the FAK/mTORC1 pathway in BMECs. SA-induced lipid synthesis, FAK/mTORC1 signaling, and the expression of lipogenic genes were impaired by anti-CD36 and the CD36-specific inhibitor SSO, whereas overexpression of CD36 effected the opposite results. Inhibition of FAK/mTORC1 by TAE226/Rapamycin attenuated SA-induced TAG synthesis, inactivated FAK/mTORC1 signaling, and downregulated the lipogenic genes PPARG, CD36, ACSL1, SCD, GPAT4, LIPIN1, and DGAT1 at the mRNA and protein levels in BMECs. By coimmunoprecipitation and yeast two-hybrid screen, CD36 interacted directly with Fyn but not Lyn, and Fyn bound directly to FAK; FAK also interacted directly with TSC2. CD36 linked FAK through Fyn, and FAK coupled mTORC1 through TSC2 to form the CD36/Fyn/FAK/mTORC1 signaling axis. Thus, stearic acid promotes lipogenesis through CD36 and Fyn/FAK/mTORC1 signaling in BMECs. Our findings provide novel insights into the underlying molecular mechanisms by which LCFA supplements promote lipid synthesis in BMECs.

Applications and Research Advances in the Delivery of CRISPR/Cas9 Systems for the Treatment of Inherited Diseases.

The rapid advancements in gene therapy have opened up new possibilities for treating genetic disorders, including Duchenne muscular dystrophy, thalassemia, cystic fibrosis, hemophilia, and familial hypercholesterolemia. The utilization of the clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases. However, the susceptibility of nucleic acid drugs to degradation by nucleic acid endonucleases necessitates the development of functional vectors capable of protecting the nucleic acids from enzymatic degradation while ensuring safety and effectiveness. This review explores the biomedical potential of non-viral vector-based CRISPR/Cas9 systems for treating genetic diseases. Furthermore, it provides a comprehensive overview of recent advances in viral and non-viral vector-based gene therapy for genetic disorders, including preclinical and clinical study insights. Additionally, the review analyzes the current limitations of these delivery systems and proposes avenues for developing novel nano-delivery platforms.

HPV Vaccination Behavior, Vaccine Preference, and Health Beliefs in Chinese Female Health Care Workers: A Nationwide Cross-Sectional Study.

Human papillomavirus (HPV) vaccination has been proven to be the most effective method to prevent cervical cancer. This study aimed to determine the HPV vaccination behavior and preference in Chinese female health care workers. A nationwide cross-sectional study was performed to recruit 15,967 respondents aged 18-45 years from 31 provinces in China's mainland in 2021. Of them, 30.0% have been vaccinated or have made an appointment. Regardless of actual vaccination status, respondents mostly preferred the 9-valent HPV vaccine (58.6%), followed by 4-valent (15.6%) and 2-valent vaccines (3.1%); additionally, 17.9% did not have a preference. Moreover, health beliefs on HPV and HPV vaccination were measured using a health belief model (HBM) analysis. Six HBM constructs differed significantly by HPV vaccination status. Higher levels of perceived susceptibility (beta = 0.074), perceived benefit (beta = 0.072), self-efficacy (beta = 0.304), and cues to action (beta = 0.039) scales were significantly associated with increasing HPV vaccine uptake. In contrast, perceived severity (beta = -0.019) and perceived barriers (beta = -0.089) were negative factors. In conclusion, HPV vaccine uptake is high in Chinese female health care workers. HBM constructs may be effective in facilitating the improvement and delivery of targeted intervention programs to increase HPV vaccine uptake.

Multi-Enzyme Cascade-Triggered Nitric Oxide Release Nanoplatform Combined with Chemo Starvation-like Therapy for Multidrug-Resistant Cancers.

Tumor drug resistance has long been a major challenge in medical oncology. Ferroptosis is a form of regulated cell death with promising clinical applications. However, the efficacy of ferroptosis-inducing agents is often limited by endogenous factors when used alone, and thus, synergistic therapy offers a promising strategy to address this issue. In this study, we developed an iron-doped metal-organic framework (MOF), Fe/ZIF-8, loaded with glucose oxidase (Gox), l-arginine (l-arg), and adriamycin hydrochloride (Dox). The folic acid (FA)-targeted ZIF-8 (GLDFe/Z-FA) prepared was shown to be a multifunctional nanoparticle based on endogenous hydrogen peroxide (H2O2) and glucose, which trigger adaptive cellular responses in cancer cells. The intracellular glucose level and adenosine-triphosphate (ATP) content decreased, indicating that GLDFe/Z-FA reduced the glucose metabolic rate and induced tumor starvation. And the generated •OH and H2O2 induced reactive oxygen species (ROS) overload to implement chemodynamic therapy (CDT). ROS catalyzed l-arg released from GLDFe/Z-FA to release nitric oxide (NO), which inhibited P-glycoprotein expression, prevented Dox efflux, and accumulated intracellular content of Dox to enhance cytotoxicity. GLDFe/Z-FA also catalyzed glutathione degradation, which further disrupted intracellular redox homeostasis, enhanced CDT, and induced cell death. It was shown to follow the ferroptosis pathway and strongly inhibited tumor proliferation both in vitro and in vivo. These findings demonstrate that GLDFe/Z-FA effectively inhibits tumor proliferation, highlighting its potential as a viable therapeutic approach to suppress cancer progression.

A Novel Bio-Adhesive Mesh System for Medical Implant Applications: In Vivo Assessment in a Rabbit Model.

Injectable surgical sealants and adhesives, such as biologically derived fibrin gels and synthetic hydrogels, are widely used in medical products. While such products adequately adhere to blood proteins and tissue amines, they have poor adhesion with polymer biomaterials used in medical implants. To address these shortcomings, we developed a novel bio-adhesive mesh system utilizing the combined application of two patented technologies: a bifunctional poloxamine hydrogel adhesive and a surface modification technique that provides a poly-glycidyl methacrylate (PGMA) layer grafted with human serum albumin (HSA) to form a highly adhesive protein surface on polymer biomaterials. Our initial in vitro tests confirmed significantly improved adhesive strength for PGMA/HSA grafted polypropylene mesh fixed with the hydrogel adhesive compared to unmodified mesh. Toward the development of our bio-adhesive mesh system for abdominal hernia repair, we evaluated its surgical utility and in vivo performance in a rabbit model with retromuscular repair mimicking the totally extra-peritoneal surgical technique used in humans. We assessed mesh slippage/contraction using gross assessment and imaging, mesh fixation using tensile mechanical testing, and biocompatibility using histology. Compared to polypropylene mesh fixed with fibrin sealant, our bio-adhesive mesh system exhibited superior fixation without the gross bunching or distortion that was observed in the majority (80%) of the fibrin-fixed polypropylene mesh. This was evidenced by tissue integration within the bio-adhesive mesh pores after 42 days of implantation and adhesive strength sufficient to withstand the physiological forces expected in hernia repair applications. These results support the combined use of PGMA/HSA grafted polypropylene and bifunctional poloxamine hydrogel adhesive for medical implant applications.

A Multifunctional Nano-Delivery System Against Rheumatoid Arthritis by Combined Phototherapy, Hypoxia-Activated Chemotherapy, and RNA Interference.

Purpose: Effective therapy for rheumatoid arthritis (RA) keeps a challenge due to the complex pathogenesis of RA. It is not enough to completely inhibit the process of RA with any single therapy method. The purpose of the research is to compensate for the insufficiency of monotherapy using multiple treatment regimens with different mechanisms. Material and Methods: In this study, we developed a new method to synthesize mesoporous silica nanoparticles hybridized with photosensitizer PCPDTBT (HNs). Branched polyethyleneimine-folic acid (PEI-FA) could be coated on the surface of HNs through electrostatic interactions. It simultaneously blocked the hypoxia-activated prodrug tirapazamine loaded into the mesopores and binded with Mcl-1 siRNA (siMcl-1) that interfered with the expression of the anti-apoptotic protein Mcl-1. Released from the co-delivery nanoparticles (PFHNs/TM) Tirapazamine and siMcl-1 upon exposure to acidic conditions of endosomes/lysosomes in activated macrophages. Under NIR irradiation, photothermal therapy and photodynamic therapy derived from PCPDTBT, hypoxia-activated chemotherapy derived from tirapazamine, and RNAi derived from siMcl-1 were used for the combined treatment for RA by killing activated macrophages. PEI-FA-coated PFHNs/TM exhibited activated macrophage-targeting characteristics, thereby enhancing the in vitro and in vivo NIR-induced combined treatment of RA. Results: The prepared PFHNs/TM have high blood compatibility (far below 5% of hemolysis) and ideal in vitro phototherapy effect while controlling the TPZ release and binding siMcl-1. We prove that PEI-FA-coated PFHNs/TM not only protect the bound siRNA but also are selectively uptaked by activated macrophages through FA receptor-ligand-mediated endocytosis, and effectively silence the target anti-apoptotic protein by siMcl-1 transfection. In vivo, PFHNs/TM have also been revealed to be selectively enriched at the inflammatory site of RA, exhibiting NIR-induced anti-RA efficacy. Conclusion: Overall, these FA-functionalized, pH-responsive PFHNs/TM represent a promising platform for the co-delivery of chemical drugs and nucleic acids for the treatment of RA cooperating with NIR-induced phototherapy.

Global research trends on precision oncology: A systematic review, bibliometrics, and visualized study.

BACKGROUND: Advances in next-generation sequencing technologies are changing the ways cancer diagnosis and treatment, which leads to a new branch of precision medicine: "Precision Oncology". This study aims to deliver a structured overview to carry out a bibliometric analysis of precision oncology research over the past 10 years retrospectively. METHODS: Bibliometric methods including clustering analysis and co-occurrence visualized study were conducted based on publications of academic databases Web of Science Main Collection from 1st January 2012, to 31st December 2021. This study analyzed the information about related research outputs, countries, institutions, authors, cited papers, and hot topics. RESULTS: 7163 papers related to precision oncology were identified. Since 2014, the number of articles has proliferated, and oncology precision has attracted significant attention from scholars worldwide in recent years. The USA leads the research in this field, and the League of European Research Universities is the primary research institution. Research institutions from Asia paid more attention to this field through high-level international cooperation. Besides, there are still many issues expected to be explored and evaluated correctly. Such as the considerable uncertainty that pharmacogenomic methods have no significant influence on patient outcomes. CONCLUSIONS: Precision oncology serves as an essential method in clinical treatment, and is closely related to biological study, including biochemistry, molecular and genetics, advanced technology, and pharmacology discovery. The future research prospect would be the broad involvement of social participation and global cooperation in oncology precision research to acquire better results via the balance of technology and public health policy.

Willingness to pay for HPV vaccine among female health care workers in a Chinese nationwide survey.

BACKGROUND: Payment methods for human papillomavirus (HPV) vaccine could substantially influence vaccination behavior. In China, HPV vaccination uptake remains currently low. This study aims to determine willingness to pay (WTP) for HPV vaccines among Chinese female health care workers under different payment scenarios. METHODS: This is a nationwide online survey recruiting female health care workers aged 18-45 years from 31 provinces throughout China. We collected the respondents' vaccination status of HPV vaccines and their sociodemographics. Two WTPs were defined and estimated in the study. A general WTP for HPV vaccination was determined using the contingent valuation method with double dichotomous choice bidding. A WTP out-of-pocket was estimated for each HPV vaccine under two scenarios, including partial coverage by governmental subsidy or partial incorporation in basic medical insurance. Accordingly, a multivariable linear regression model was employed to determine the association between sociodemographis and general WTP. Then the maximum WTP out-of-pocket was compared among the respondents' attitude shift towards HPV vaccination, payment scenarios, and levels of vaccine attributes, using non-parametric Kruskal-Wallis test. RESULTS: A total of 15,969 respondents were included in the study. The median general WTP was 2000 CNY (interquartile range, 1000-3200 CNY), positively associated with younger age, unmarried status, higher monthly income, fewer children, more positive vaccination behavior, working in tertiary hospital, higher local GDP and HDI (each P < 0.05). Moreover, the median WTP out-of-pocket was 1250 CNY (540-2000 CNY). It was significantly higher for vaccines partly covered by governmental subsidy (median, 1250 CNY; interquartile range, 560-2000 CNY), imported vaccines (1260 CNY; 630-1960 CNY), and 9-valent vaccines (1400 CNY; 750-2240 CNY) (each P < 0.001). Additionally, majority of respondents did not change their attitude towards HPV vaccination between two payment scenarios; those remaining with more expensive HPV vaccines (51.1%) had higher WTP out-of-pocket (1400 CNY; 560-2250 CNY) than those with cheaper vaccines (39.0%) (1120 CNY; 490-1960 CNY) (P < 0.001). CONCLUSION: Chinese female health care workers have high WTP for HPV vaccines. A direct public funding for HPV vaccination is more preferable. Our findings may facilitate the adjustment of HPV vaccination strategy and payment mechanism in China.

Protective effects of chlorogenic acid on inflammatory responses induced by Staphylococcus aureus and milk protein synthesis in bovine mammary epithelial cells.

Staphylococcus aureus (S. aureus) is a major mastitis-causing pathogen in dairy cows. Dairy cows with mastitis suffer from a decrease in milk yield and protein content. Chlorogenic acid (CGA) is a natural product with anti-inflammatory effects. In this study, we examined the function and mechanism of CGA with regard to its anti-inflammatory effects and evaluated its protective function in milk protein synthesis in bovine mammary epithelial cells (BMECs). BMECs were cultured with and without infection by S. aureus and CGA, and extracellular inflammatory cytokines and amino acids in the medium and milk proteins were determined by ELISA. The function of IL-10RA in anti-inflammatory processes and of SF-1 in milk protein synthesis was assessed by gene silencing. The activity of mTORC1, NF-κB, and STAT5 was examined by western blot. S. aureus caused intracellular infection and upregulated TNF-α, IL-1ß, IL-6, and IL-8, whereas uptake of amino acids and milk protein synthesis were suppressed. CGA mitigated the S. aureus-induced inflammatory response and milk protein synthesis in vitro and in vivo. CGA alleviated S. aureus-induced inhibition of mTORC1 and STAT5 and upregulated IL-10 and IL-10RA. In addition, SF-1 was predicted to be a transcription factor of the milk protein-encoding genes α-LA, ß-LG, and CSN2. S. aureus downregulated SF-1 and CGA reversed the decline in milk protein synthesis due to SF-1 knockdown. Thus, CGA mitigates the inflammatory response that is induced by S. aureus and protects the uptake of amino acids and milk protein synthesis in BMECs.

Multifactor Analysis and Intervention Study on Menstrual Disorders of Female Athletes in the Context of the Winter Olympic Games: A Case-Control Study Based on a Large Sample.

A case-control study was conducted to explore the multifactor analysis and intervention of menstrual disorders in female athletes under the background of the Winter Olympic Games, which is based on a large sample. For this purpose, from January 2020 to September 2021, 381 female athletes in long-term ice and snow sports were investigated by random sampling. All of them promoted gynecological examination and counted the incidence of menstrual disorders. The subjects were assigned into two groups according to their menstrual status: abnormal (n = 163) and normal menstrual state groups (n = 218). The basic and clinical data of the two groups were compared, and univariate analysis and multivariate logistic regression analysis were employed to explore the risk factors of menstrual disorders in female athletes. According to the random number table method, the menstrual disorder group was again assigned into the intervention group and the control group. The intervention group received health education and glucose supplement intervention to correct EAMDs, while the control group only received health education. The improvement of patients' ability balance and the changes of reproductive hormones were compared after intervention. The results of univariate analysis indicated that there exhibited no significant differences in age, menarche age, smoking history, drinking history, grade, sexual life history, abortion history, BMI, and location of household registration, but there were significant differences in family history, sleep quality, diet regularity, and mental health status (P < 0.05). The results of univariate analysis indicated that there exhibited no significant differences in age, menarche, smoking, drinking, grade, sexual life history, abortion history, family history, sleep quality, diet regularity, and mental health status. Logistic regression analysis indicated that family history of menstrual disorders, poor sleep quality, irregular diet, and mental health status all affected women's menstrual disorders (OR: 1.411, 95% CI: 1.378∼1.444; OR: 1.501, 95% CI: 1.030∼2.187; OR: 1.554, 95% CI: 1.086∼2.225; OR: 1.383, 95% CI: 1.018∼1.877, respectively) independent risk factors. According to the comparison of menstrual cycle, in the intervention group, 12 patients had menstrual cycle 21-28 days, 12 patients had menstrual cycle 28-38 days, and 58 patients were irregular and had no amenorrhea, while in the control group, 36 patients had menstrual cycle 21-28 days, 24 patients had 28-38 days, 12 patients had amenorrhea, and 11 patients had irregular menstruation, and there exhibited no significant difference (P > 0.05). There exhibited no significant difference in energy balance before and after intervention (P > 0.05); after intervention, the ability balance of the two groups was significantly promoted, and the degree of improvement in the study group was better (P < 0.05). The indexes of reproductive hormones in the follicular phase were compared before and after glucose supplement intervention, and there exhibited no significant difference before intervention (P > 0.05); after intervention, the serum LH and GnRH of the two groups decreased, while FSH and P increased. The improvement degree of the intervention group was better than that of the control group, but there exhibited no significant difference (P > 0.05). Before intervention, there exhibited no significant difference in the serum E2 level in the follicular phase (P > 0.05); after the intervention, the serum E2 of the two groups increased significantly, and the improvement of the intervention group was better (P < 0.05). Before intervention, there exhibited no significant difference in the serum E2 level in the follicular phase (P > 0.05); after the intervention, the serum E2 of the two groups increased significantly, and the improvement of the intervention group was better (P < 0.05). Before intervention, there exhibited no significant difference in serum E2 and P levels in the luteal phase (P > 0.05); after intervention, the level of serum E2 decreased and the level of serum P increased in the two groups. There exhibited no significant difference in the level of serum E2 (P > 0.05). There exhibited significant difference in the serum P level (P < 0.05). Female athletes have a high rate of menstrual disorders. Family history of menstrual disorders, poor sleep quality, irregular diet, and poor mental health are the main risk factors of menstrual disorders. Health education and sugar supplement intervention measures for female athletes play a positive role in the improvement of their ability balance and the regulation of reproductive hormones.

Honokiol nanosuspensions loaded thermosensitive hydrogels as the local delivery system in combination with systemic paclitaxel for synergistic therapy of breast cancer.

Local administration of therapeutic agents provides a favorable approach to enhance drug accumulation at pathological sites. In this study, a novel honokiol nanosuspensions loaded thermosensitive injectable hydrogels (HK-NS-Gel) was designed as the local delivery system for the combination therapy with systemic paclitaxel (PTX). The formed HK-NS-Gel showed superior gelation time and temperature. In vitro release and in vivo drug retention assay showed that HK-NS-Gel can slowly and steadily release the HK during 12 days. Meanwhile, enhanced PTX accumulation in the tumor was observed after intratumoral injection of HK-NS-Gel. In vitro cytotoxicity and cell apoptosis tests against 4T1 cells proved the synergistic effects of free PTX combined with HK-NS-Gel. In vivo antitumor study was conducted on 4T1 bearing mice, indicating that co-administration HK-NS-Gel and PTX could effectively enhance tumor growth suppression, and the tumor inhibitory rate was as high as 72.51%. In conclusion, intravenous delivery of PTX combined with intratumoral delivery of HK-NS-Gel was a promising combination for breast cancer therapy with enhanced therapeutic response and safety.

Analyzing material changes consistent with degradation of explanted polymeric hernia mesh related to clinical characteristics.

BACKGROUND: Proposed mechanisms that potentially contribute to polypropylene mesh degradation after in vivo exposure include oxidizing species and mechanical strains induced by normal healing, tissue integration, muscle contraction, and the immediate and chronic inflammatory responses. METHODS: This study explores these potential degradation mechanisms using 63 mesh implants retrieved from patients after a median implantation time of 24 months following hernia repair surgery (mesh explants) and analysis of multivariate associations between the material changes and clinical characteristics. Specifically, polypropylene mesh degradation was characterized in terms of material changes in surface oxidation, crystallinity and mechanical properties, and clinical characteristics included mesh placement location, medical history and mesh selection. RESULTS: Compared to pristine control samples, subsets of mesh explants had evidence of surface oxidation, altered crystallinity, or changed mechanical properties. Using multivariate statistical approach to control for clinical characteristics, infection was a significant factor affecting changes in mesh stiffness and mesh class was a significant factor affecting polypropylene crystallinity changes. CONCLUSIONS: Highly variable in vivo conditions expose mesh to mechanisms that alter clinical outcomes and potentially contribute to mesh degradation. These PP mesh explants after 0.5 to 13 years in vivo had measurable changes in surface chemistry, crystallinity and mechanical properties, with significant trends associated with factors of mesh placement, mesh class, and infection.

Exploring the Potential Mechanism of Artemisinin and Its Derivatives in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking.

Objective: This study is aimed at predicting and contrasting the mechanisms of artemisinin (ARS), dihydroartemisinin (DHA), artesunate (ART), artemether (ARM), and arteether (ARE) in the treatment of osteoporosis (OP) using network pharmacology and molecular docking. Methods: The targets of ARS, DHA, ART, ARM, and ARE were obtained from the SwissTargetPrediction. The targets related to OP were obtained from the TTD, DrugBank, Genecards, and DisGeNet databases. Then, the anti-OP targets of ARS, DHA, ART, ARM, and ARE were obtained and compared using the Venn diagram. Afterward, the protein-protein interaction (PPI) networks were built using the STRING database, and Cytoscape was used to select hub targets. Moreover, molecular docking validated the binding association between five molecules and hub targets. Finally, GO enrichment and KEGG pathway enrichment were conducted using the DAVID database. The common pathways of five molecules were analysed. Results: A total of 28, 37, 36, 27, and 33 anti-OP targets of ARS, DHA, ART, ARM, and ARE were acquired. EGFR, EGFR, CASP3, MAPK8, and CASP3 act as the top 1 anti-OP targets of ARS, DHA, ART, ARM, and ARE, respectively. MAPK14 is the common target of five molecules. All five molecules can bind well with these hubs and common targets. Meanwhile, functional annotation showed that MAPK, Serotonergic synapse, AMPK, prolactin, and prolactin signaling pathways are the top 1 anti-OP pathway of ARS, DHA, ART, ARM, and ARE, respectively. IL-17 signaling pathway and prolactin signaling pathway are common anti-OP pathways of five molecules. Besides, GO enrichment showed five biological processes and three molecular functions are common anti-OP mechanisms of five molecules. Conclusion: ARS, DHA, ART, ARM and ARE can treat OP through multi-targets and multi pathways, respectively. All five molecules can treat OP by targeting MAPK14 and acting on the IL-17 and prolactin signaling pathways.

A Review of 3D Printing in Dentistry: Technologies, Affecting Factors, and Applications.

Three-dimensional (3D) printing technologies are advanced manufacturing technologies based on computer-aided design digital models to create personalized 3D objects automatically. They have been widely used in the industry, design, engineering, and manufacturing fields for nearly 30 years. Three-dimensional printing has many advantages in process engineering, with applications in dentistry ranging from the field of prosthodontics, oral and maxillofacial surgery, and oral implantology to orthodontics, endodontics, and periodontology. This review provides a practical and scientific overview of 3D printing technologies. First, it introduces current 3D printing technologies, including powder bed fusion, photopolymerization molding, and fused deposition modeling. Additionally, it introduces various factors affecting 3D printing metrics, such as mechanical properties and accuracy. The final section presents a summary of the clinical applications of 3D printing in dentistry, including manufacturing working models and main applications in the fields of prosthodontics, oral and maxillofacial surgery, and oral implantology. The 3D printing technologies have the advantages of high material utilization and the ability to manufacture a single complex geometry; nevertheless, they have the disadvantages of high cost and time-consuming postprocessing. The development of new materials and technologies will be the future trend of 3D printing in dentistry, and there is no denying that 3D printing will have a bright future.

Indocyanine Green-Parthenolide Thermosensitive Liposome Combination Treatment for Triple-Negative Breast Cancer.

BACKGROUND: Certain patients with triple-negative breast cancer cannot tolerate the serious adverse effects of cytotoxic chemotherapy agents, which significantly affect the disease prognosis. PURPOSE: Research into the combined use of photosensitizers and non-cytotoxic antineoplastic drugs for the safe treatment of triple-negative breast cancer is vital. METHODS: In this study, the photosensitizer indocyanine green and the natural drug parthenolide were co-loaded into thermosensitive liposomes. Under a near-infrared irradiation, indocyanine green reached excitation levels, releasing heat, and the liposome underwent a phase transition, releasing the drug were researched. RESULTS: Thus, indocyanine green and parthenolide exert synergistic antineoplastic effects. In the nude mice xenograft MDA-MB-231 tumor model, the tumor inhibition rate of indocyanine green-parthenolide thermosensitive liposomes was approximately 2.08-fold than that of paclitaxel and demonstrated a good initial safety evaluation. CONCLUSION: Photosensitizers and non-cytotoxic antineoplastic agents in combination with nanoscale carriers should be further investigated for the treatment of tumors.

Surface modification of polypropylene surgical meshes for improving adhesion with poloxamine hydrogel adhesive.

Tissue adhesive has notable clinical benefits in hernia repair fixation. A novel poloxamine tissue adhesive was previously shown to successfully bond collagen tissue with adequate adhesive strength. In application related to attachment of polypropylene (PP) mesh, the adhesive strength between the mesh and poloxamine hydrogel adhesive is limited by the hydrophobicity of PP monofilaments and lack of covalent bond formation. The purpose of this study was to compare two different surface modifications [bovine serum albumin (BSA) adsorption and poly-glycidyl methacrylate/human serum albumin (PGMA/HSA) grafting] of PP mesh for improving the adhesive strength between poloxamine hydrogel adhesive and PP mesh. The PGMA/HSA surface modification significantly improved the adhesive strength for meshes attached with poloxamine hydrogel tissue adhesive compared with unmodified meshes and meshes modified by BSA adsorption. An area of 1 cm2 adhesive provided for a maximum adhesive strength of 65-70 kPa for meshes modified by PGMA/HSA, 4-13 kPa for meshes modified by BSA, and 22-45 kPa for unmodified meshes. Optical microscopy and infrared spectroscopy (FTIR) confirmed the improved adhesive strength was achieved through mechanical interlock of the hydrogel tissue adhesive into the PP mesh pores and chemical bonding of the albumin after successful PGMA/HSA grafting onto the PP monofilaments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1047-1055, 2019.

Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice: bone marrow and small intestine.

BACKGROUND: Our previous research demonstrated that one subcutaneous injection of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) 24 hours (h) before irradiation (8.75 Gy) increased mouse survival by 75%. However, the protective mechanism of 17-DMAG is currently unknown. The present study aimed to investigate whether oral administration of 17-DMAG was also radioprotective and the potential role it may play in radioprotection. RESULTS: A single dose of orally pre-administered (24, 48, or 72 h) 17-DMAG (10 mg/kg) increased irradiated mouse survival, reduced body weight loss, improved water consumption, and decreased facial dropsy, whereas orally post-administered 17-DMAG failed. Additional oral doses of pre-treatment did not improve 30-day survival. The protective effect of multiple pre-administrations (2-3 times) of 17-DMAG at 10 mg/kg was equal to the outcome of a single pre-treatment. In 17-DMAG-pretreated mice, attenuation of bone marrow aplasia in femurs 30 days after irradiation with recovered expressions of cluster of differentiation 34, 44 (CD34, CD44), and survivin in bone marrow cells were observed. 17-DMAG also elevated serum granulocyte-colony stimulating factor (G-CSF), decreased serum fms-related tyrosine kinase 3 ligand, and reduced white blood cell depletion. 17-DMAG ameliorated small intestinal histological damage, promoted recovery of villus heights and intestinal crypts including stem cells, where increased leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) was found 30 days after irradiation. CONCLUSIONS: 17-DMAG is a potential radioprotectant for bone marrow and small intestine that results in survival improvement.

Decay-accelerating factor attenuates C-reactive protein-potentiated tissue injury after mesenteric ischemia/reperfusion.

BACKGROUND: C-reactive protein (CRP) is an acute pro-inflammatory mediator that has been demonstrated to enhance ischemia/reperfusion (IR) injury by virtue of activating the complement system. CRP is able to interact with complement proteins such as C1q, complement factor H, and C4b-binding protein. Since complement activation is central in the expression of tissue injury following IR, we have investigated the effects of human decay-accelerating factor (DAF), a complement inhibitor, on CRP-potentiated complement activation and tissue injury in mice subjected to mesenteric IR. MATERIALS AND METHODS: Male C57B1/6 mice were allocated into eight groups: (1) Sham-operated group without IR injury; (2) CRP+Sham group; (3) IR group; (4) CRP+IR group; (5) DAF group; (6) CRP+DAF group; (7) IR+DAF group, and (8) CRP+IR+DAF group. Intestinal and lung injury, neutrophil infiltration, myeloperoxidase (MPO) expression, complement component deposition, and interleukin-6 (IL-6) production were assessed for each treatment group of mice. RESULTS: We report that administration of DAF significantly attenuates the CRP-enhanced intestinal injury as well as remote lung damages following acute mesenteric IR in mice, while DAF inhibits complement activation, suppresses neutrophil infiltration, and reduces IL-6 production. CONCLUSIONS: Our study suggests that inhibition complement activation with DAF may prove useful for the treatment of post-ischemic inflammatory injuries associated with an increased production of CRP.