Prospective study of urinary incontinence recovery following endoscopic enucleation of the prostate.

OBJECTIVE: To investigate the clinical trajectories and identify risk factors linked to post-enucleation urinary incontinence (UI). PATIENTS AND METHODS: In this prospective study (April 2020 to March 2022) at a single institution, 316 consecutive patients receiving endoscopic enucleation due to benign prostatic enlargement were included. Patient information and perioperative details were collected. Follow-ups, from 1 to 6 months, assessed postoperative UI using International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and a four-item pad questionnaire, classified per International Continence Society definitions. Logistic regression analysed predictors at 1 week, while generalised estimating equation assessed risk factors from 1 to 3 months postoperatively. RESULTS: Patients with a median prostate volume of 57 mL underwent enucleation, with 22.5% experiencing postoperative UI at 1 week, 5.6% at 3 months, decreasing to 1.9% at 6 months. Multivariable analysis identified age (>80 years), specimen weight (>70 g), en bloc with anteroposterior dissection, and anal tone (Digital Rectal Examination Scoring System score <3) as potential factors influencing UI. Subgroup analysis revealed that specimen weight was associated with both continuous and stress UI. Anal tone was related to both other types and stress UI, while overactive bladder symptoms were associated with urge UI. CONCLUSION: In summary, our study elucidates transient risk factors contributing to temporary post-enucleation UI after prostatectomy. Informed decisions and personalised interventions can effectively alleviate concerns regarding postoperative UI.

Emulsion template fabricated heterogeneous bilayer gelatin-based scaffolds with sustained-delivery of lycium barbarum glycopeptide for periodontitis treatment.

Periodontitis is a chronic inflammatory disease raising the risks of tooth-supporting structures destruction and even tooth loss. The way to reconstruct periodontal bone tissues in inflammatory microenvironment has been long in demand for periodontitis treatment. In this study, the lycium barbarum glycopeptide (LbGP) loaded gelatin-based scaffolds were fabricated for periodontitis treatment. Gelatin microspheres with suitable size were prepared by emulsification and gathered by oxidized sodium alginate to prepare heterogeneous bilayer gelatin-based scaffolds, and then they were loaded with LbGP. The prepared scaffolds possessed interconnected porous microstructures, good degradation properties, sufficient mechanical properties, sustained release behavior and well biocompatibility. In vitro experiments suggested that the LbGP loaded gelatin-based scaffolds could inhibit the expression of inflammatory factors (IL-1ß, IL-6, and TNF-α), promote the expression of anti-inflammatory factor (IL-10), and the expression of osteogenic markers (BMP2, Runx2, ALP, and OCN) in PDLSCs under the LPS-stimulated inflammatory microenvironment. Moreover, in rat periodontitis models, the LbGP gelatin-based scaffolds would reduce the alveolar bone resorption of rats, increase the collagen fiber content of periodontal membrane, alleviate local inflammation and improve the expression of osteogenesis-related factors. Therefore, the LbGP loaded gelatin-based scaffolds in this study will provide a potential therapeutic strategy for periodontitis treatment.

Emulsion template fabricated gelatin-based scaffold functionalized by dialdehyde starch complex with antibacterial antioxidant properties for accelerated wound healing.

Gelatin and starch are considered as promising sustainable materials for their abundant production and good biodegradability. Efforts have been made to explore their medical application. Herein, scaffolds based on gelatin and starch with a preferred microstructure and antibacterial antioxidant property were fabricated by the emulsion template method. The dialdehyde starch was firstly combined with silver nanoparticles and curcumin to carry out the efficient hybrid antibacterial agent. Then, the gelatin microsphere of appropriate size was prepared by emulsification and gathered by the above agent to obtain gelatin-based scaffolds. The prepared scaffolds showed porous microstructures with high porosity of over 74 % and the preferred pore sizes of ∼65 µm, which is conducive to skin regeneration. Moreover, the scaffolds possessed a good swelling ability of over 640 %, good degradability of over 18 days, excellent blood compatibility, and cell compatibility. The promising antibacterial and antioxidant properties came from the hybrid antibacterial agent were affirmed. As expected, the gelatin-based scaffolds fabricated by the emulsion template method with a preferred microstructure can facilitate more adhered fibroblasts. In summary, gelatin-based scaffolds functionalized by starch-based complex expanded the application of abundant sustainable materials in the biomedical field, especially as antibacterial antioxidant wound dressings.

Comparison of senhance and da vinci robotic radical prostatectomy: short-term outcomes, learning curve, and cost analysis.

BACKGROUND: The Senhance® Robotic System is a new laparoscopy-based platform that has been increasingly used in radical prostatectomy (RP) procedures. The purpose of this study is to compare the outcome of Senhance RP (SRP) with da Vinci RP (DRP) cases. METHODS: From August 2019 to April 2022, we prospectively recruited 63 cases of SRP. We compared the perioperative data, postoperative complication rates, short-term surgical outcomes (3-month postoperative undetectable prostate-specific antigen (PSA) and incontinence rates), learning curves, and cost analysis with data from 63 matched da Vinci Xi RP cases. RESULTS: There was no difference in BL (180 versus 180 ml, p = 0.86) and postoperative surgical complication rate (Clavient -Dindo grade I-IV, 25.3 versus 22.2%, p = 0.21) between the SRP cases and the DRP. Regarding the oncologic and continence function, there was no difference between positive margin rate (36.5% versus 41.3%, p = 0.58), rate of undetectable PSA level at postoperative 3 months (68.3 versus 66.7%, p = 0.85), and incontinence rate (14.3 versus 15.9%, p = 1.0) at postoperative 3 months between the two cohorts. The learning curve showed a quick downward slope for laparoscopic experienced surgeons. The median pocket cost for SRP patients in our hospital was $4170, which was lower than $7675 for the DRP patients. CONCLUSIONS: Safety and short-term outcomes are comparable between SRP and DRP. For experienced LRP surgeons, using the Senhance system to perform RP is straightforward. With a more affordable price as its biggest advantage, the Senhance system may serve as a safe and effective alternative for robotic RP.

A SARS-CoV-2-specific CAR-T-cell model identifies felodipine, fasudil, imatinib, and caspofungin as potential treatments for lethal COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced cytokine storm is closely associated with coronavirus disease 2019 (COVID-19) severity and lethality. However, drugs that are effective against inflammation to treat lethal COVID-19 are still urgently needed. Here, we constructed a SARS-CoV-2 spike protein-specific CAR, and human T cells infected with this CAR (SARS-CoV-2-S CAR-T) and stimulated with spike protein mimicked the T-cell responses seen in COVID-19 patients, causing cytokine storm and displaying a distinct memory, exhausted, and regulatory T-cell phenotype. THP1 remarkably augmented cytokine release in SARS-CoV-2-S CAR-T cells when they were in coculture. Based on this "two-cell" (CAR-T and THP1 cells) model, we screened an FDA-approved drug library and found that felodipine, fasudil, imatinib, and caspofungin were effective in suppressing the release of cytokines, which was likely due to their ability to suppress the NF-κB pathway in vitro. Felodipine, fasudil, imatinib, and caspofungin were further demonstrated, although to different extents, to attenuate lethal inflammation, ameliorate severe pneumonia, and prevent mortality in a SARS-CoV-2-infected Syrian hamster model, which were also linked to their suppressive role in inflammation. In summary, we established a SARS-CoV-2-specific CAR-T-cell model that can be utilized as a tool for anti-inflammatory drug screening in a fast and high-throughput manner. The drugs identified herein have great potential for early treatment to prevent COVID-19 patients from cytokine storm-induced lethality in the clinic because they are safe, inexpensive, and easily accessible for immediate use in most countries.

Risk of cognitive impairment in men with advanced prostate cancer treated with NHAs: A systematic review and network meta-analysis.

Novel hormonal agents (NHAs) have significantly improved outcomes in men with advanced prostate cancer. However, it remains unclear whether NHAs are associated with subsequent cognitive impairment. Thus, we sought to perform a network meta-analysis to compare the risk of cognitive impairment across NHA types. Databases (PubMed, Embase, Scopus, and Web of Science), trial registries (Clinicaltrial.gov), the European Medicines Agency, and the US Food and Drug Administration drug safety reports were searched from inception through July 30, 2021. Eligible studies were clinical trials evaluating the risk of cognitive impairment between NHAs and placebo/standard care. Two independent investigators extracted the data and performed quality assessments using the Cochrane Risk of Bias Tool and ROBINS-I. We estimated the risk ratios by the frequentist approach and calculated the ranking probabilities of all treatments with the surface under the cumulative ranking probabilities. The primary outcome and secondary outcome were odds ratio (OR) and incidence rate ratio of cognitive impairment, respectively. We identified 15 trials with 14,723 participants comparing HNAs with placebo/standard care. Treatments associated with cognitive impairment, from the most to the least, were enzalutamide (OR, 3.66; 95% confidence interval [CI], 2.84-4.73), apalutamide (OR, 1.76; 95% CI, 1.08-2.87), abiraterone acetate (OR, 1.64; 95% CI, 1.01-2.45), and darolutamide (OR, 1.11 95% CI, 0.51-2.39). After adjustment of treatment time duration, enzalutamide still had the highest risk of cognitive impairment with an incidence rate ratio of 2.17 (95% CI, 1.65-2.78). These findings suggest that NHAs, especially enzalutamide, may increase the risk of cognitive impairment compared with placebo/standard care.

Matrix metalloproteinase-responsive collagen-oxidized hyaluronic acid injectable hydrogels for osteoarthritic therapy.

Drug delivery system and intra-articular injection have been clinically applied to prolong drug residence time and reduce side effects in the treatment of osteoarthrosis. Herein, injectable hydrogels with sustained-dexamethasone sodium phosphate (DSP) release behavior in response to matrix metalloproteinase (MMP) were developed for osteoarthritic therapy. Hyaluronic acid undergoes specific oxidation in the present of sodium periodate to prepare oxidized hyaluronic acid (OHA). Then the DSP-loaded collagen-based hydrogels (Col-OHA) were developed by the Schiff's base crosslinking between OHA and Type I collagen besides the self-assembly of collagen induced by OHA. The results indicate that the collagen self-assembly into collagen fibrils makes great contribution for shortening gelation time of Col-OHA hydrogels. Col-OHA hydrogels possess interconnected porous microstructure, good injectability, excellent self-healing performance, strong mechanical property, low swelling ability, good blood compatibility and no cytotoxicity. Significantly, Col-OHA hydrogels show highly sensitive and significantly substantially sustained release of DSP in response to MMP. DSP-loaded Col-OHA hydrogel possesses significant inhibition for the production of inflammatory cytokines in the joint synovium, which can effectively relieve the symptoms of osteoarthritis continuously. Col-OHA hydrogel has no obvious effect on liver and kidney functions. Overall, the Col-OHA hydrogels with excellent biocompatibility are the promising drug-loading system for the intra-articular injection therapy of osteoarthrosis.

Crosslinking effect of dialdehyde cholesterol modified starch nanoparticles on collagen hydrogel.

Crosslinking is frequently used to improve the inherent poor physicochemical properties of collagen. However, local flocculation and irregular crosslinking of collagen would be unavoidably occurred once contacting with crosslinking agents due to widespread complex interactions. Herein, dialdehyde starch-based nanoparticles were developed to crosslink collagen as a new strategy. Starch was conjugated with cholesterol chloroformate before periodate oxidation to obtain dialdehyde cholesterol modified starch (DACS). DACS self-assembled into nanoparticles (DACSNPs) and crosslinked with collagen to fabricate collagen hydrogels (DACSNPs-Col). DACSNPs-Col hydrogels exhibited faster gelation rate, better uniform porous structure, higher mechanical properties and better degradation stability than dialdehyde starch crosslinked hydrogels. Significantly, DACSNPs-Col hydrogels show homogeneous structure, improved mechanical properties, low cytotoxicity, well blood compatibility, high cell adhesion and proliferation. Overall, the oxidized polysaccharide nanoparticles crosslinked collagen hydrogels have homogeneous and compact microstructure and improved physicochemical properties, which show potential application prospect in the field of tissue engineering scaffold.

Predicting nanoemulsion formulation and studying the synergism mechanism between surfactant and cosurfactant: A combined computational and experimental approach.

Nanoemulsion (NE) is a dosage form widely used in pharmaceutical, food, agrochemical, cosmetics, and personal care industries. NE systems are usually formulated through trial and error via numerous semi-empirical experiments. Moreover, the complex interaction mechanisms between the formulation surfactant and cosurfactant are difficult to understand. Dissipative particle dynamics (DPD) may be helpful in solving these formulation problems. Silibinin is a flavonolignan isolated from milk thistle, which has demonstrated antioxidant and antimicrobial effects. For this project, silibinin-loaded nanoemulsion (SBNE) was formulated by DPD, including surfactant and cosurfactant screening, pseudo-ternary phase construction, and SBNE characterization, all of which were verified by experimentation. Most importantly, this work shows that DPD can be adopted to explore the synergetic mechanisms between the surfactant and cosurfactant, including emulsification efficiency, distance, angle, arrangement, and order parameter. Additional verification experiments on the antioxidant and antimicrobial applications of simulation-designed SBNE were also carried out and confirmed DPD-predicted results. As such, predicting NE formulation by DPD has been proven to be feasible. For SBNE, the addition of PEG400 cosurfactant stretches the Cremophor RH40 surfactant molecules and assists in a more orderly arrangement. An enhanced interfacial thickness in SBNE could be attributed to the stretched hydrophilic head group and the decreased angle between the molecular axis and interface normal. These DPD and experimentally-verified results indicated that a proper cosurfactant will enhance the interfacial thickness, decrease the consumption of surfactant, and benefit NE formation. This new computationally applied knowledge should facilitate optimizing, designing, and understanding NE formulation more rationally and scientifically.

Mimicking the Composition and Structure of the Osteochondral Tissue to Fabricate a Heterogeneous Three-Layer Scaffold for the Repair of Osteochondral Defects.

Heterogeneous three-layer scaffolds were fabricated by mimicking the biochemical composition and structure of the hyaline cartilage, calcified cartilage, and subchondral bone of the osteochondral tissue for the repair of osteochondral defects. The hyaline cartilage layer was composed of collagen I (50.0 wt %) and sodium hyaluronate (50.0 wt %). The calcified cartilage layer and subchondral bone layer were composed of collagen I, sodium hyaluronate, and nanohydroxyapatite with different proportions. N-Hydroxysuccinimide/N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride was used to mediate the crosslinking reaction of the amine groups of collagen with carboxyl groups of sodium hyaluronate. The hyaline cartilage layer and calcified cartilage layer were designed as dense structures, while the subchondral bone layer was designed as a relatively loose structure by adjusting the crosslinking degree. The scaffolds displayed a uniform and interconnected porous structure and possessed a high porosity over 85%, which were conducive to cellular adhesion and proliferation. The scaffolds could remain at 50-75% after 30 days of degradation owing to crosslinking, providing enough time for the regeneration of the osteochondral tissue. Especially, the hyaline cartilage layer and calcified cartilage layer preferred to induce the proliferation of chondrocytes, while the subchondral bone layer was more conducive to the proliferation of osteoblasts. In conclusion, the heterogeneous multilayer scaffolds could serve as implant materials for osteochondral reconstruction.

pH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy.

pH-Responsive nanoparticles (NPs) have emerged as an effective antitumor drug delivery system, promoting the drugs accumulation in the tumor and selectively releasing drugs in tumoral acidic microenvironment. Herein, we developed a new amphiphilic modified hydroxyethyl starch (HES) based pH-sensitive nanocarrier of antitumor drug delivery. HES was first modified by hydrophilic imidazole and hydrophobic cholesterol to obtain an amphiphilic polymer (IHC). Then IHC can self-assemble to encapsulate doxorubicin (DOX) and form doxorubicin-loaded nanoparticles (DOX/IHC NPs), which displayed good stability for one week storage and acidic sensitive long-term sustained release of DOX. As a result, cancer cell endocytosed DOX/IHC NPs could continuously release doxorubicin into cytoplasm and nucleus to effectively kill cancer cells. Additionally, DOX/IHC NPs could be effectively enriched in the tumor tissue, showing enhanced tumor growth inhibition effect compared to free doxorubicin. Overall, our amphiphilic modified HES-based NPs possess a great potential as drug delivery system for cancer chemotherapy.

Functionalization of an Electroactive Self-Healing Polypyrrole-Grafted Gelatin-Based Hydrogel by Incorporating a Polydopamine@AgNP Nanocomposite.

Hydrogels are considered a promising wound dressing owing to their ability to absorb wound exudates and their moist network structure for skin regeneration. It is of great significance to give added multiple functions to hydrogels for wound healing. In this paper, we present a gelatin-based hydrogel with self-healing ability, conductivity, and antibacterial and antioxidant activities. Dopamine was added into an alkaline solution to polymerize into polydopamine (PDA), which was used to reduce AgNO3 into Ag nanoparticles (AgNPs) to gain a PDA@AgNP composite. Polypyrrole-grafted gelatin (PPyGel) was dissolved in a PDA@AgNP solution and ferric ions were used as a cross-linking agent to form PDA@AgNPs-PPyGel-Fe hydrogels. The as-prepared hydrogels are soft and ductile and exhibit porous structures with pore sizes from 20 to 50 µm. The hydrogels have high water absorption ability, indicating the potential to absorb wound exudates. PPy and Fe3+ endow the hydrogels with slightly higher conductivity than that of skin tissue, indicating the ability to effectively transmit bioelectric signals for skin regeneration. The ionic interactions and hydrogen bonding in hydrogels make them possess self-healing ability, and the self-healing process can be completed in 30 min. PDA confers hydrogels with effective antioxidant activities, while AgNPs endow hydrogels with good antibacterial activities. Moreover, the hydrogels possess good blood compatibility and cytocompatibility. In sum, the developed hydrogel has potential applications as wound dressings.

Controlling the Pore Structure of Collagen Sponge by Adjusting the Cross-Linking Degree for Construction of Heterogeneous Double-Layer Bone Barrier Membranes.

Guided bone regeneration (GBR) has been regarded as a valuable way to effectively induce bone remodeling. The key factor of GBR is to place a barrier membrane between the soft tissue and bone defect, preventing the untimely intrusion of fibroblasts and permitting the prior settlement of internal osteoblasts. Notably, heterogeneous double-layer GBR membranes with a compact upper layer and a loose lower layer exhibit enhanced effectiveness in blocking fibroblasts and promoting the growth of osteoblasts. Herein, we present porous and interconnected collagen-based sponges with controllable pore size for the fabrication of absorbable GBR membranes with a heterogeneous double-layer structure. Dialdehyde carboxymethyl cellulose was used to fix collagen-based sponges. The pore size of the sponges can be well controlled by adjusting the cross-linking degree, which is decreased with an increase of cross-linking degree. The sponges show enhanced mechanical properties, inhibited swelling ability and biodegradation, good blood compatibility, and good cytocompatibility. The sponges are feasible to form a heterogeneous double-layer structure with a loose lower layer and a compact upper layer. Interestingly, the lower layer with the pore size of 200-300 µm can promote the adhesion, proliferation, and differentiation of osteoblasts MC3T3-E1 cells, while the upper layer with the pore size of 20-50 µm makes a great contribution to the growth of myoblast C2C12 cells. Overall, the collagen-based sponges have the potential to be used to fabricate heterogeneous double-layer bone barrier membranes for bone remodeling.

Emulsion Template Method for the Fabrication of Gelatin-Based Scaffold with a Controllable Pore Structure.

The porous microstructure of scaffolds is an essential consideration for tissue engineering, which plays an important role for cell adhesion, migration, and proliferation. It is crucial to choose optimum pore sizes of scaffolds for the treatment of various damaged tissues. Therefore, the proper porosity is the significant factor that should be considered when designing tissue scaffolds. Herein, we develop an improved emulsion template method to fabricate gelatin-based scaffolds with controllable pore structure. Gelatin droplets were first prepared by emulsification and then solidified by genipin to prepare gelatin microspheres. The microspheres were used as a template for the fabrication of porous scaffolds, which were gathered and tightened together by dialdehyde amylose. The results showed that emulsification can produce gelatin microspheres with narrow size distribution. The size of gelatin microspheres was easily controlled by adjusting the concentration of gelatin and the speed of mechanical agitation. The gelatin-based scaffolds presented macroporous and interconnected structure. It is interesting that the pore size of scaffolds was directly related to the size of gelatin microspheres, displaying the same trend of change in size. It indicated that the gelatin microspheres can be used as the proper template to fabricate gelatin-based scaffold with a desired pore structure. In addition, the gelatin-based scaffolds possessed good blood compatibility and cytocompatibility. Overall, the gelatin-based scaffolds exhibited great potential in tissue engineering.

Development of Microspheres Based on Thiol-Modified Sodium Alginate for Intestinal-Targeted Drug Delivery.

Bioactive peptide drugs are mostly delivered by parenteral administration, which brings great pain and risks to patients. Oral administration is an acceptable alternative form. However, peptide drugs are extremely sensitive to the strong acidic environment in the stomach after oral administration. They would be degraded by pepsin and trypsin in the gastrointestinal tract. Herein, we present microspheres for intestinal-targeted peptides drug delivery through oral administration. Sodium alginate was reacted with l-cysteine to bring it into thiol groups. Then sodium alginate-l-cysteine conjugates were mixed with native sodium alginate and emulsified by an improved method. Ca2+ was used to fix the emulsion to get the microspheres. Bovine serum albumin was used as the simulating drug to assess the feasibility of microspheres as intestinal delivery carriers. The results showed that the microspheres exhibited spherical properties and narrow size distribution. The drug-loading capacity of microspheres was not compromised after thiol-modification. It is interesting that the microspheres can maintain structural integrity and hold drugs in the strong acidic environment in the stomach. Conversely, the microspheres presented sustained intestinal-targeted drugs release ability as expected. Moreover, thiol-modification further improved the adherence ability of microspheres on the inner walls of the small intestine, which is good for enhancing drug permeability. In sum, the microspheres based on thiol-modified sodium alginate have promising applications as intestinal-targeted macromolecular drug carriers.

3D-QSAR pharmacophore-based virtual screening, molecular docking and molecular dynamics simulation toward identifying lead compounds for NS2B-NS3 protease inhibitors.

NS2B-NS3 protease has been identified to serve as lead drug design target due to its significant role in West Nile viral (WNV) and dengue virus (DENV) reproduction and replication. There are currently no approved chemotherapeutic drugs and effective vaccines to inhibit DENV and WNV infections. In this work, 3D-QSAR pharmacophore model has been developed to discover potential inhibitory candidates. Validation through Fischer's model and decoy test indicate that the developed 3D pharmacophore model is highly predictive for DENV inhibitors, which was then employed to screen ZINC chemical library to obtain reasonable hits. Following ADMET filtering, 15 hits were subjected to further filter through molecular docking and CoMFA modeling. Finally, top three hits were identified as lead compounds or potential inhibitory candidates with IC50 values of ∼0.4637 µM and fitness of ∼57.73. It is implied from CoMFA modeling that substituents at the side site of benzotriazole such as a p-nitro group (e.g. biphenyl head) and a carbonyl (e.g. carboxylate function) at the side site of furan or amino group may improve bioactivity of ZINC85645245, respectively. Molecular dynamics simulations (MDS) were performed to discover new interactions and reinforce the binding modes from docking for the hits also. The QSAR and MDS results obtained from this work should be useful in determining structural requirements for inhibitor development as well as in designing more potential inhibitors for NS2B-NS3 protease.

A novel toolbox for the in vitro assay of hepatitis D virus infection.

Hepatitis D virus (HDV) is a defective RNA virus that requires the presence of hepatitis B virus (HBV) for its life cycle. The in vitro HDV infection system is widely used as a surrogate model to study cellular infection with both viruses owing to its practical feasibility. However, previous methods for running this system were less efficient for high-throughput screening and large-scale studies. Here, we developed a novel method for the production of infectious HDV by adenoviral vector (AdV)-mediated transduction. We demonstrated that the AdV-based method yields 10-fold higher viral titers than the transient-transfection approach. The HDV-containing supernatant derived from AdV-infected Huh7 cells can be used as the inoculum in infectivity assays without requiring further concentration prior to use. Furthermore, we devloped a chemiluminescent immunoassay (HDV-CLEIA) to quantitatively determine intracellular HDAg with a dynamic range of 5-11,000 pg/mL. HDV-CLEIA can be used as an alternative approach to assess HDV infection. The advantages of our updated methodology were demonstrated through in vitro HDV infection of HepaRG cells and by evaluating the neutralization activity using antibodies that target various regions of the HBV/HDV envelope proteins. Together, the methods presented here comprise a novel toolbox of in vitro assays for studying HDV infection.

Prolonged suppression of HBV in mice by a novel antibody that targets a unique epitope on hepatitis B surface antigen.

OBJECTIVE: This study aimed to investigate the therapeutic potential of monoclonal antibody (mAb) against HBV as a novel treatment approach to chronic hepatitis B (CHB) in mouse models. METHODS: Therapeutic effects of mAbs against various epitopes on viral surface protein were evaluated in mice mimicking persistent HBV infection. The immunological mechanisms of mAb-mediated viral clearance were systematically investigated. RESULTS: Among 11 tested mAbs, a novel mAb E6F6 exhibited the most striking therapeutic effects in several HBV-persistent mice. Single-dose administration of E6F6 could profoundly suppress the levels of hepatitis B surface antigen (HBsAg) and HBV DNA for several weeks in HBV-transgenic mice. E6F6 regimen efficiently prevented initial HBV infection, and reduced viral dissemination from infected hepatocytes in human-liver-chimeric mice. E6F6-based immunotherapy facilitated the restoration of anti-HBV T-cell response in hydrodynamic injection (HDI)-based HBV carrier mice. Immunological analyses suggested that the Fcγ receptor-dependent phagocytosis plays a predominant role in E6F6-mediated viral suppression. Molecular analyses suggested that E6F6 recognises an evolutionarily conserved epitope (GPCK(R)TCT) and only forms a smaller antibody-viral particle immune complex with limited interparticle crosslinking when it binds to viral particles. This unique binding characteristic of E6F6 to HBV was possibly associated with its effective in vivo opsonophagocytosis for viral clearance. CONCLUSIONS: These results provided new insight into understanding the therapeutic role and mechanism of antibody against persistent viral infection. The E6F6-like mAbs may provide a novel immunotherapeutic agent against human chronic HBV infection.

Preparation, physicochemical characterization and release behavior of the inclusion complex of trans-anethole and ß-cyclodextrin.

Trans-anethole (AT) has a variety of antimicrobial properties and is widely used as food functional ingredient. However, the applications of AT are limited due to its low water solubility, strong odor and low physicochemical stability. Therefore, the aim of this work was to encapsulate AT with ß-cyclodextrin (ß-CD) for obtaining inclusion complex by co-precipitation method. The measurements effectively confirmed the formation of inclusion complex between AT and ß-CD. The results showed that the inclusion complex presented new solid crystalline phases and was more thermally stable than the physical mixture and ß-CD. The phase solubility study showed that the aqueous solubility of AT was increased by being included in ß-CD. The calculated stability constant of inclusion complex was 1195M-1, indicating the strong interaction between AT and ß-CD. Furthermore, the release study suggested that ß-CD provided the protection for AT against evaporation. The release behavior of AT from the inclusion complex was controlled.

Vibratory perception and female stress urinary incontinence.

PURPOSE: We investigated the value of measuring the vibratory perception threshold with a biothesiometer to clinically evaluate women with stress urinary incontinence. MATERIALS AND METHODS: The study consisted of 3 groups, including group 1--66 women with stress urinary incontinence, group 2--44 age matched women without stress urinary incontinence and group 3--60 younger women without stress urinary incontinence. A total of 50 patients with stress urinary incontinence underwent videourodynamics. Using a biothesiometer the vibratory perception threshold was measured over the middle finger, middle toe and clitoris in all study subjects. A higher threshold indicated lower sensitivity to vibratory stimulation. Motions leading to stress urinary incontinence were also determined. RESULTS: The stress urinary incontinence and age matched control groups were older than the younger control group and had greater parity. The incontinence group had a higher vibratory perception threshold than the younger control group but there was no difference between women with incontinence and age matched women without incontinence. Women in whom incontinence was induced by walking upstairs or downstairs had a higher finger and toe vibratory perception threshold than those without incontinence. The threshold in the groups with and without intrinsic sphincter deficiency did not differ significantly. CONCLUSIONS: Vibratory perception is not related to stress urinary incontinence in females. Finger and toe vibratory perception is less sensitive in patients with stress urinary incontinence while walking upstairs or downstairs.