Wnt4 regulates bone metabolism through IKK-NF-κB and ROCK signaling under occlusal traumatic periodontitis.

BACKGROUND AND OBJECTIVE: Occlusal trauma is one of the most important local contributing factors of periodontitis. It has been reported that Wnt4, a noncanonical Wnt ligand, can inhibit osteoclast formation and inflammation and promote bone formation in vivo. However, the prospects of Wnt4 application in occlusal trauma and periodontitis have not yet been described. This study aimed to investigate the function and the corresponding mechanism of Wnt4 to regulate bone metabolism in occlusal trauma and periodontitis. MATERIAL AND METHODS: Osteogenic-induced MC3T3-E1 cells were treated with or without Porphyromonas gingivalis lipopolysaccharide (Pg. LPS) under cyclic uniaxial compressive stress. After treatment with mouse recombinant protein Wnt4 (rWnt4), the expression of osteogenic markers and activation of the IKK-NF-κB signaling pathway were evaluated in vitro. To investigate whether Wnt4 can promote osteogenesis via the ROCK signaling pathway, the expression of RhoA was evaluated in vitro. Finally, we evaluated the change in bone quantity and the activation of the IKK-NF-κB and ROCK signaling in mice with occlusal trauma and periodontitis to demonstrate the therapeutic efficacy of rWnt4 injection. RESULTS: Stimulation of traumatic force and Pg. LPS stimulation suppressed the expression of osteoblast markers, but their expression was rescued after rWnt4 treatment in vitro. In addition, the inhibition of the ROCK signaling pathway induced by force loading was reversed when rWnt4 was applied in vitro. Micro-CT, H&E, and TRAP staining of the mandibles showed increased bone loss in the occlusal trauma-aggravated periodontitis group, whereas it was rescued after rWnt4 injection. The expression levels of IκBα and p65 were upregulated in occlusal trauma and periodontitis-bearing mice, whereas the expression levels of Runx2 and RhoA were downregulated. After rWnt4 injection, remarkably upregulation of Runx2 and RhoA expression was observed in occlusal trauma and periodontitis- bearing mice. CONCLUSION: Wnt4 not only inhibits IKK-NF-κB signaling but also activates ROCK signaling to inhibit osteoclast formation and promote bone regeneration in occlusal trauma and periodontitis-bearing mice.

Flow-through enzymatic reactors using polymer monoliths: From motivation to application.

The application of monolithic materials as carriers for enzymes has rapidly expanded to the realization of flow-through analysis and bioconversion processes. This expansion is partly attributed to the absence from diffusion limitation in many monoliths-based enzyme reactors. Particularly, the relatively ease of introducing functional groups renders polymer monoliths attractive as enzyme carriers. After summarizing the motivation to develop enzymatic reactors using polymer monoliths, this review reports the most recent applications of such reactors. Besides, the present review focuses on the crucial characteristics of polymer monoliths affecting the immobilization of enzymes and the processing parameters dictating the performance of the resulting enzymatic reactors. This review is intended to provide a guideline for designing and applying flow-through enzymatic reactors using polymer monoliths.

Variants in STAT4 Associated With Cure of Chronic HBV Infection in HBeAg-positive Patients Treated With Pegylated Interferon-alpha.

BACKGROUND & AIMS: Variants in STAT4 (rs7574865) have been associated with seroconversion to hepatitis B e antigen (HBeAg) and reduction in levels of hepatitis B virus (HBV) DNA in patients with chronic infection treated with interferon alpha (IFNA). We evaluated the associations among rs7574865, loss of HB surface antigen (HBsAg, a marker of functional cure of HBV infection), and response to treatment with pegylated IFNA (PegIFN) or nucleos(t)ide analogues (NUCs) in HBeAg-positive patients with chronic HBV infection. METHODS: We performed a retrospective analysis of 1823 HBeAg-positive patients with chronic HBV infection (954 patients treated with PegIFN and 869 patients treated with NUCs) included in 4 phase-4 multicenter randomized controlled trials. The Cochran-Armitage trend test was used to evaluate the association of rs7574865 genotype with combined response (CR, defined as HBeAg seroconversion and HBV DNA level <2000 IU/mL) and loss of HBsAg at week 72, for patients given PegIFN, or week 104, for patients given NUCs. RESULTS: We found a significant association between rs7574865 genotype and CR (P = .004) and loss of HBsAg (P = .037) in patients treated with PegIFN. In patients with HBV genotype B infection, 43.6% of those with rs7574865 TT achieved a CR, compared to patients with rs7574865 GG (20.5%), and 7.7% had loss of HBsAg, compared to 1.9% of patients with rs7574865 GG. However, in patients treated with NUCs, we found no association of rs7574865 genotype with CR (P = .811) or loss of HBsAg (P=.439). CONCLUSIONS: In a retrospective analysis of data from 4 clinical trials, we found rs7574865 in STAT4 to be associated with functional cure of chronic HBV infection by PegIFN treatment, but not NUCs treatment, in HBeAg-positive patients with HBV genotype B infection.

Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues.

OBJECTIVE: The investigation regarding the clinical significance of quantitative hepatitis B core antibody (anti-HBc) during chronic hepatitis B (CHB) treatment is limited. The aim of this study was to determine the performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive CHB patients treated with peginterferon (Peg-IFN) or nucleos(t)ide analogues (NUCs), respectively. DESIGN: This was a retrospective cohort study consisting of 231 and 560 patients enrolled in two phase IV, multicentre, randomised, controlled trials treated with Peg-IFN or NUC-based therapy for up to 2 years, respectively. Quantitative anti-HBc evaluation was conducted for all the available samples in the two trials by using a newly developed double-sandwich anti-HBc immunoassay. RESULTS: At the end of trials, 99 (42.9%) and 137 (24.5%) patients achieved HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. We defined 4.4 log10 IU/mL, with a maximum sum of sensitivity and specificity, as the optimal cut-off value of baseline anti-HBc level to predict HBeAg seroconversion for both Peg-IFN and NUC. Patients with baseline anti-HBc ≥4.4 log10 IU/mL and baseline HBV DNA <9 log10 copies/mL had 65.8% (50/76) and 37.1% (52/140) rates of HBeAg seroconversion in the Peg-IFN and NUC cohorts, respectively. In pooled analysis, other than treatment strategy, the baseline anti-HBc level was the best independent predictor for HBeAg seroconversion (OR 2.178; 95% CI 1.577 to 3.009; p<0.001). CONCLUSIONS: Baseline anti-HBc titre is a useful predictor of Peg-IFN and NUC therapy efficacy in HBeAg-positive CHB patients, which could be used for optimising the antiviral therapy of CHB.

Response-guided peginterferon therapy in patients with HBeAg-positive chronic hepatitis B: A randomized controlled study.

BACKGROUND & AIMS: Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the pegylated interferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B. METHODS: In this open-label, multicenter, randomized trial, HBeAg positive patients were treated with PegIFN (180µg/week) for 24weeks. Early responders (HBsAg <1500IU/ml and HBV DNA <10(5)copies/ml at week 24) received PegIFN for a further 24weeks (arm A), while non-early responders were randomized to PegIFN for another 24weeks (arm B), another 72weeks (arm C) or PegIFN for another 72weeks plus adefovir for 36weeks (arm D). The primary endpoint was the change of quantitative HBsAg from baseline to the end of follow-up (EOF). RESULTS: For non-early responders, 96-week PegIFN monotherapy did not lead to a greater reduction of HBsAg from baseline to EOF, compared with 48-week PegIFN (-0.71 vs. -0.67log10IU/ml, P=0.407). The rate of HBeAg seroconversion with HBV DNA <2000IU/ml at EOF were similar for arms B, C and D (17.9%, 23.9% and 25.0% respectively). For patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24, 38.4% and 37.0% achieved HBeAg seroconversion with HBV DNA <2000IU/ml at EOF respectively. CONCLUSIONS: Patients with HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml at week 24 would benefit from continued PegIFN treatment. Extending the duration of PegIFN with or without adding adefovir did not show superiority over 48weeks PegIFN monotherapy. LAY SUMMARY: Extending the duration of pegylated interferon (PegIFN) alfa-2a is not recommended in HBeAg positive patients as treatment extension beyond 48weeks did not show convincing benefit. Patients who achieved HBsAg <1500IU/ml or HBV DNA <10(5)copies/ml after 24-week PegIFNα-2a showed satisfactory outcome after the withdrawal of finite PegIFNα-2a treatment. CLINICAL TRIAL NUMBER: NCT01086085.

Development of atom transfer radical polymer-modified gold nanoparticle-based enzyme-linked immunosorbent assay (ELISA).

In this work, a novel enzyme-linked immunosorbent assay (ELISA) with a low limit of detection and high sensitivity was developed using atom transfer radical polymer (ATRP)-modified gold nanoparticles (AuNPs). Clear signal amplification was achieved by introducing an abundance of horseradish peroxidase (HRP) to the AuNPs, because of the ATRP modification. This result suggested that the new ELISA was able to detect antigens in complex mixtures, and the limit of detection (LOD) was lower than that of conventional ELISA by a factor of 81. The new ELISA strategy greatly decreased the LOD during analysis and exhibited excellent reproducibility, stability, and feasibility. Therefore, it is a promising technique with many potential applications in biochemistry and medical science research.

Advances in Functionalized Hydrogels in the Treatment of Myocardial Infarction and Drug-Delivery Strategies.

Myocardial infarction (MI) is a serious cardiovascular disease with high morbidity and mortality rates, posing a significant threat to patient's health and quality of life. Following a MI, the damaged myocardial tissue is typically not fully repaired, leading to permanent impairment of myocardial function. While traditional treatments can alleviate symptoms and reduce pain, their ability to repair damaged heart muscle tissue is limited. Functionalized hydrogels, a broad category of materials with diverse functionalities, can enhance the properties of hydrogels to cater to the needs of tissue engineering, drug delivery, medical dressings, and other applications. Recently, functionalized hydrogels have emerged as a promising new therapeutic approach for the treatment of MI. Functionalized hydrogels possess outstanding biocompatibility, customizable mechanical properties, and drug-release capabilities. These properties enable them to offer scaffold support, drug release, and tissue regeneration promotion, making them a promising approach for treating MI. This paper aims to evaluate the advancements and delivery methods of functionalized hydrogels for treating MI, while also discussing their potential and the challenges they may pose for future clinical use.

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

Effects of combined exogenous dextranase and sodium fluoride on Streptococcus mutans 25175 monospecies biofilms.

PURPOSE: To investigate the effects of exogenous dextranase and sodium fluoride on a S. mutans monospecies biofilm. METHODS: S. mutans 25175 was grown in tryptone soya broth medium, and biofilm was formed on glass slides with 1.0% sucrose. Exogenous dextranase and sodium fluoride were added alone or together. The biofilm morphology was analyzed by confocal laser scanning microscopy. The effects of the drug on the adhesion and exopolysaccharide production by the biofilms were evaluated by scintillation counting and the anthrone method, respectively. RESULTS: In this study, we found that the structure of initial biofilm and mature biofilm were partly altered by dextranase and high concentrations of sodium fluoride separately. However, dextranase combined with a low concentration of sodium fluoride could clearly destroy the typical tree-like structure of the biofilm, and led to less bacterial adhesion than when the dextranase or fluoride were used alone (P < 0.05). The amounts of soluble and insoluble exopolysaccharide were significantly reduced by combining dextranase with a low concentration of sodium fluoride, much more than when they were used alone (P < 0.05). These data indicate that dextranase and a low concentration of sodium fluoride may have synergistic effects against S. mutans biofilm and suggest the application of a low concentration of sodium fluoride in anticaries treatment.

[Liver histopathological features influencing HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B responding to Peg-IFN treatment].

OBJECTIVE: To investigate the therapeutic efficiency of antiviral treatment with pegylated-interferon (Peg-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) and to explore whether liver histopathological features or other factors influence the HBeAg seroconversion treatment response. METHODS: Eighty HBeAg-positive CHB patients with diagnosis confirmed by liver puncture were treated with Peg-IFN(2a or 2b)body weight dose, once weekly). At treatment week 48, the rate of HBeAg seroconversion was determined and used to analyze the influence of liver histopathological features (liver biopsy assessment of: inflammation, graded G0 to G4; fibrosis stage, graded S0 to S4), sex, age, differential levels (pre-treatment baseline vs. week 48 post-treatment) of serum alanine transferase (ALT), and HBV DNA, by binary logistic analysis. RESULTS: At week 48, the overall rate of HBeAg seroconversion was 30.0%. The rate of HBeAg seroconversion gradually advanced with increased liver inflammation (X2 = 8.435, P = 0.015): 9.09% of the 22 patients with G1; 31.58% of the 38 patients with G2; 47.30% of the 19 patients with G3; the one patient with G4. In contrast, the rate of HBeAg seroconversion showed a much weaker association with liver fibrosis (X2 = 5.917, P = 0.116). Only baseline HBeAg level, and no other baseline index, was significantly different between the patients who achieved HBeAg seroconversion and those who did not. Liver inflammation and baseline HBeAg level were identified as influencing factors of HbeAg seroconversion in response to Peg-IFN treatment. CONCLUSION: Peg-IFN therapy induces a higher rate of HBeAg seroconversion in HBeAg-positive CHB patients with severe liver inflammation; histological analysis of pre-treatment liver biopsies may help to identify patients most likely to benefit from the antiviral regimen.

Green process for isolation and purification of poly(ß-L-malic acid) from Aureobasidium spp. by an integrated ion exchange and membrane separation.

Poly (ß-L-malic acid) (PMLA) is a biopolymer used in food and medical fields. However, the industrial processes are susceptible to the pollution of CaSO4 waste and organic solvent owing to the heavy use of CaCO3 in fermentation process and organic solvents in isolation process. This study developed an organic solvent and CaSO4 -free process for the industrial-scale production of PMLA. Firstly, calcium ion was removed at pH 9.2 by pH adjustment with Na2CO3, and the generated CaCO3 was reused in the fermentation process. Then, the D296 resin was selected to isolate the PMLA from the Ca2+-free broth, where the adsorption data were both primely described by the Freundlich and Langmuir equation, while Freundlich model better fit the process than Langmuir equation, indicating that it was non-monolayer adsorption of PMLA on the resin. Meanwhile, a three-step gradient elution with phosphate buffer (i.e., 0.2 mol/L, pH 7.0) containing 0.1, 0.2 and 1 mol/L NaCl was developed to recover PMLA. Finally, a PES15 membrane was selected to recover the PMLA from the elution solution, which could be reused in the next cycle. As a result, the PMLA with a purity of 98.89 % was obtained with the developed green process. In the developed process, it removed the pollution of organic solvent and calcium waste for the biosynthesis of PMLA on an industrial scale, which also offers a sustainable and green route for the biosynthesis of other carboxylic acids.

Fractionation and characterization of poly(ß-L-malic acid) produced by Aureobasidium melanogenum ipe-1.

Poly (ß-L-malic acid) (PMLA) is attracting industrial interest for its potential application in medicine and other industries, whose functions primarily depend upon its molecular size and chemical structure. Up to now, the fractionation and characterization of PMLA produced by Aureobasidium spp. were still unclear. In this study, the product from A. melanogenum ipe-1 was effectively fractionated using 300 and 50 kDa membranes. During the filtration, the mechanisms of membrane fouling were illegible since the PMLA can both reject and permeate the membrane, while the main fouling mechanism varied between standard blocking and complete blocking during the diafiltration. After fractionation, 14.0, 8.4 and 77.6 % of the PMLAs with Mws of 75,134, 21,344 and 10,056 Da were distributed in the 300 kDa retentate after diafiltrating, 50 kDa retentate after diafiltrating, and the 50 kDa permeate, respectively. The Mw/Mns of the PMLAs were 4.12, 1.92, and 1.12 in the three fractions. Based on characteristic spectra of NMR, HPLC and FTIR, the product was not usual L-malic acid monomers, but glucose-terminated PMLA. The glucose was located at the terminal hydroxyl of PMLA. These results would serve as a valuable guide for process design and practical operation in subsequent industrial application.

Prevention and management of drug resistant hepatitis B virus infections.

In the past decade, broadened therapeutic options of oral direct antiviral agents for the treatment of chronic hepatitis B infection include: Lamivudine, Adefovir Dipivoxil, Telbivudine, Entecavir and Tenofovir Disoproxil Fumarate. These direct oral antiviral agents effectively suppress the replication of the virus and reduce the risk of potential liver-related complications. However, prolonged use of these nucleos(t)ide analogues has been associated with drug resistance that compromises the initial clinical benefits. Moreover, the oncogenic risk of mutations due to prolonged nucleos(t)ide analogue therapy needs to be further investigated by in vitro and in vivo studies. In the current era of potent nucleotide analogues, new data are emerging, we are still facing the pool of patients who have developed resistance to the prior generation of nucleos(t)ide analogues. This paper aims to focus on incidence of antiviral drug resistance and virological breakthrough, prudent selection of initial therapy, on-treatment monitoring for drug resistance and revise treatment strategies for patients with resistant virus.

Three Dimensional Printing of Bioinspired Crossed-Lamellar Metamaterials with Superior Toughness for Syntactic Foam Substitution.

Biological materials such as conch shells with crossed-lamellar textures hold impressive mechanical properties due to their capability to realize effective crack control and energy dissipation through the structural synergy of interfacial modulus mismatch and lamellar orientation disparity. Integrating this mechanism with mechanical metamaterial design can not only avoid the catastrophic post-yield stress drop found in traditional architectural materials with uniform lattice structures but also effectively maintain the stress level and improve the energy absorption ability. Herein, a novel bioinspired design strategy that combines regional particularity and overall cyclicity is proposed to innovate the connotation of long-range periodicity inside the metamaterial, in which the node constraint gradient and crossed-lamellar struts corresponding to the core features of conch shells are able to guide the deformation sequence with a self-strengthening response during compression. Detailed in situ experiments and finite element analysis confirm that the rotated broad layer stacking can shorten and impede the shear bands, further transforming the deformation of bioinspired metamaterial into a progressive, hierarchical way, highlighted by the cross-layer hysteresis. Even based on a brittle polymeric resin, excellent specific energy absorption capacity [4544 kJ/kg] has been achieved in this architecture, which far exceeds the reported metal-based syntactic foams for two orders of magnitude. These results offer new opportunities for the bioinspired metamaterials to substitute the widespread syntactic foams in specific applications required for both lightweight and energy absorption.

Williams Syndrome With Rare Ureteric Abnormality.

Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by infantile hypercalcemia, short stature, a varying degree of mental retardation, elfin-like facial features, and cardiovascular abnormalities, including systemic hypertension, aortic hypoplasia, coarctation of the aorta, and valvular heart disease (aortic and pulmonic stenosis, mitral valve prolapsed or bicuspid aortic valve). It is also characterized by friendly and outgoing personality. The majority of WS cases are sporadic, while few are familial. Both sporadic and familial cases are due to deletion of chromosome 7 (7q11.23). Herein, we present an autopsy case of a 16-day-old male infant born to a 25-year-old mother with a history of William syndrome. Prenatal echocardiogram showed supravalvular aortic stenosis and pulmonary stenosis. The postnatal course was complicated by feeding difficulties and desaturation. Gross autopsy findings included generalized edema, macrocephaly with short neck, and multiple facial anomalies (mandibular hypoplasia, depressed nasal bridge, long philtrum, ear malformation, and wide mouth). The heart was hypertrophied with obstructed ventricles and rudimentary, hypoplastic aortic root. An enlarged, dilated, and tortuous left ureter was a unique finding to this case, in addition to variation in the renal arteries' size and an small bowel outpouching located 33 cm from the ileocecal valve. Cytogenetic analysis revealed deletion of chromosome 7 (7q11.23). In conclusion, majority of WS cases are sporadic, and few are familial and are inherited as autosomal dominant.

Preparation of Anisotropic Micro-Hydrogels with Tunable Structural and Topographic Features by Compound Interfacial Shearing.

We propose a compound interfacial shearing (CIS) process for versatile production of monodisperse Janus emulsions with controllable structural and topographic features. The process induces an active periodic force to decouple material and process parameters, enables independent control of compartmental features in Janus emulsions, and facilitates inline and on-demand generation of various geometric features for a large variety of process parameters and material properties. Janus emulsions of poly(ethylene glycol) diacrylate (PEGDA) with a controlled number of compartments are produced by CIS and photopolymerized to form micro-hydrogels with designated interfacial curvatures. PEGDA micro-hydrogels can be further modified to achieve anisotropy of surface or internal features by the content of an oily dispersed phase. MCF-7 human breast cancer cells are encapsulated in micro-hydrogels for cell proliferation with satisfactory viability. By modifying PEGDA micro-hydrogels with RGDS-conjugated polystyrene microspheres, we have demonstrated the controlled spatial adhesion of MCF-7 cells and human umbilical vein endothelial cells (HUVECs) on the substrates of different three-dimensional (3D) curvatures. Our pilot study suggests a simple and potentially scalable approach to produce 3D substrates with controllable structural and topographic features for 3D guided cell organization.

A photo-responsive membrane for tailored drug delivery with spatially and temporally controlled release.

Accurate delivery of therapeutics to tumor regions and effective sparing of normal tissue structures are important principles for the treatment of widespread metastases or malignant lesions in close proximity to vital organs. However, the currently available drug delivery techniques do not support precise drug release within the identified disease margins. We propose a tailored drug delivery strategy that utilizes a photo-responsive material in combination with tumor margin imaging for automated and tailored release of therapeutics. As a proof of concept, a poly(ethylene oxide)-b-PSPA (PEO-b-PSPA) diblock copolymer is synthesized by spiropyran (SP) polymerization. A photo-responsive membrane (PRM) is formed and irradiated with light sources of different wavelengths. Switching irradiation between ultraviolet light (UV) and green light (Vis) controls the permeability of the PRM in coincidence with the programmed irradiation patterns. The dynamic process of photo-switchable drug permeation through the PRM is modeled and compared with the experimental results. The strategy of tailored drug release is verified using both regular geometric shapes and metastatic cancer images. The therapeutic effect of this tailored drug release strategy is demonstrated in vitro in human breast cancer cells. Our pilot study implies the technical potential of using photo-responsive carriers for image-guided chemotherapy with precisely controlled drug release patterns.

Gualou Xiebai Banxia decoction ameliorates Poloxamer 407-induced hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis. OBJECTIVE: The present study aimed to examine GLXBBX's preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats. MATERIALS AND METHODS: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats' plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected. RESULTS: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1). CONCLUSION: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.

Magnetic Targeting and Ultrasound Activation of Liposome-Microbubble Conjugate for Enhanced Delivery of Anticancer Therapies.

Effective delivery of chemotherapeutics with minimal toxicity and maximal outcome is clinically important but technically challenging. Here, we synthesize a complex of doxorubicin (DOX)-loaded magneto-liposome (DOX-ML) microbubbles (DOX-ML-MBs) for magnetically responsive and ultrasonically sensitive delivery of anticancer therapies with enhanced efficiency. Citrate-stabilized iron oxide nanoparticles (MNs) of 6.8 ± 1.36 nm were synthesized, loaded with DOX in the core of oligolamellar vesicles of 172 ± 9.2 nm, and covalently conjugated with perfluorocarbon (PFC)-gas-loaded microbubbles to form DOX-ML-MBs of ∼4 µm. DOX-ML-MBs exhibited significant magnetism and were able to release chemotherapeutics and DOX-MLs instantly upon exposure to ultrasound (US) pulses. In vitro studies showed that DOX-ML-MBs in the presence of US pulses promoted apoptosis and were highly effective in killing both BxPc-3 and Panc02 pancreatic cancer cells even at a low dose. Significant reduction in the tumor volume was observed after intravenous administration of DOX-ML-MBs in comparison to the control group in a pancreatic cancer xenograft model of nude mice. Deeply penetrated iron oxide nanoparticles throughout the magnetically targeted tumor tissues in the presence of US stimulation were clearly observed. Our study demonstrated the potential of using DOX-ML-MBs for site-specific targeting and controlled drug release. It opens a new avenue for the treatment of pancreatic cancer and other tissue malignancies where precise delivery of therapeutics is necessary.