Identification of hyperglycemia-associated microbiota alterations in saliva and gingival sulcus.

Oral microbes are a contributing factor to hyperglycemia by inducing an increase in insulin resistance resulting in uncontrolled blood glucose levels. However, the relationship between the distribution of oral flora and hyperglycemia is still controversial. Combining the power of MALDI-Biotyper with anaerobic bacterial culture, this study explores the correlation between anaerobic bacteria in the oral cavity and blood glucose levels. The results demonstrated that altered blood glucose levels contributed to a varied bacterial distribution in the oral cavity. Specifically, Veillonella spp. and Prevotella spp. were identified in a higher proportion in people with elevated blood glucose levels. Six bacterial species identified in this study (Prevotella melaninogenica, Campylobacter rectus, Streptococcus gordonii, Streptococcus mitis, Streptococcus salivarius, and Veillonella parvula) not only demonstrated a positive association with higher blood glucose levels, but also likely contribute to the development of the condition. The data demonstrated MALDI-TOF MS to be a simpler, faster, and more economical clinical identification tool that provides clarity and depth to the research on blood glucose and oral microbiota.

Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations.

Hot melt extrusion (HME), a technology which mixing the advantages of solid dispersion technology and mechanical preparation, is accepted in varied applications in pharmaceutical formulations. When combined with other techniques, such as nanotechnique, three-dimensional printing, and co-extrusion, HME becomes much more multifunctional in the application of drug delivery. While in most cases, polymers employed in HME are responsible for the final property of products. The process of HME together with the selection of materials employed in HME were described briefly. In addition, the applications of HME in drug delivery and its currently status in the pharmaceutical field were also included. Some commercial products produced by HME have met the approval of FDA, indicating the commercial viability of this technique. Although showing great potential in pharmaceutical manufacturing, HME is still challenged by high temperature, shear force, and high input energy. Development of equipment, modifying the parameters, and optimization of polymeric formulations are needed for a safe, effective, and multifunctional hot melt extrusion drug delivery system. Also, wider range of combinations between HME and other techniques may provide guideline for developing multiple applications in drug delivery.

Stereocomplexed electrospun nanofibers containing poly (lactic acid) modified quaternized chitosan for wound healing.

Skin damage, especially the extensive full-thickness wound, is seriously affecting people's daily life and health. Meanwhile, wound healing is always challenged by bacterial infection. In this study, for the purpose of developing a disinfectant wound dressing, we designed a novel multi-functional nanofiber mats via electrospinning combining chitosan derivations and stereocomplex crystallite (SC). The SC membrane of poly (lactic acid)/chitosan derivatives were prepared via warming at 80 °C for 1 h. The thermal and mechanical properties of the heated mats were strengthened owing to the formation of SC, which restricted the lactide chains mobility. In vivo wound healing test revealed that the SC mats have better wound repair ability than the control group with a wound healing rate of 100 % within 15 days. In a word, the biomass-based mats with enhanced thermal and mechanical properties, antibacterial effect and antioxidant activity, providing a potential multi-functional platform for designing of disinfectant wound dressings.

Potent Anti-adhesion Barrier Combined Biodegradable Hydrogel with Multifunctional Turkish Galls Extract.

Clinically, postoperative adhesions are common and serious complications, which almost always happen after abdominal or pelvic surgery. The adhesion development process is accompanied by increased inflammatory cell infiltration and oxygen-free radical production. In this study, the naturally occurring antioxidative and anti-inflammatory compounds extracted from Turkish galls by ethyl acetate (GEA) were encapsulated into an injectable and biodegradable thermosensitive hydrogel. Antiadhesion efficacy of the barrier system (GEA-NP/H) was tested on a rat peritoneum injury-cecum abrasion model. Upon injection, the mildly viscous liquid formed a potent physical barrier over the injured cecum and peritoneum without any additional cross-linkers or light sources. Once formed, GEA-NP/H acted as a durable wound dressing for more than 5 days, as well as a sustained drug depot of GEA. The polymer hydrogel can be degraded and absorbed gradually. After 14 days, severe adhesion occurred among rats treated with normal saline and GEA-loaded nanoparticles (GEA-NP). Whereas, frequency of score 1 adhesion among the blank hydrogel group is 30%, and 90% of the rats from GEA-NP/H group exhibited no adhesion. In addition, pathological sections and scanning electron microscopy assay demonstrated that operative defects treated with GEA-NP/H suffered from mild oxidative stress and inflammatory damages at early days after injury, as well as accelerated wound healing and more mature mesothelial cell deposition at the 14th day in contrast to the blank hydrogel treatment. Therefore, the study provided an available biodegradable hydrogel barrier to effectively prevent postsurgical adhesion.

Strengthened and Thermally Resistant Poly(lactic acid)-Based Composite Nanofibers Prepared via Easy Stereocomplexation with Antibacterial Effects.

Strengthened poly(lactic acid) (PLA)-based materials with improved mechanical performance and improved thermal resistance, notably, are prepared by introducing stereocomplex crystallite (SC), an ideal filler, into the materials. Owing to the intermolecular hydrogen bond among the stereoisomer chains, the melting point of the special crystallite is up to 200 °C, which is 50 °C higher than the isostatic crystallite. The modulus of the PLA-based materials can be enhanced to several 100 MPa because of the integrated polymer chain arrangement. In this study, we electrospun hybrid nanofibers consisted of PLA stereoisomers and induced the stereocomplex crystallization under a mild condition (65 °C for 1 h). The mild warming is favorable for the protection of chlorogenic acid (CA) that was selected as the antibacterial agent. Both of Gram-positive and Gram-negative bacteria were efficiently cleared away using the warmed nanofibers that released CA rapidly within just a few hours. Used as filters, the SC electrospinning membrane also presented a potent filtering effect, leaving no bacteria retained in the filtrates. Attributing to SC, the PLA-based nanofibers showed extremely increased melting temperature over 200 °C and improved Young's modulus up to 270.0 MPa. The durable nanofibers prepared in present study are meaningful for enlarging the application of PLA-based materials, for example, as filters, masks, and packages.

Improving the pharmacokinetics and tissue distribution of pyrinezolid by self-assembled polymeric micelles.

Antibiotic-resistance by bacteria is a growing global concern within the healthcare field, and it has provided an impetus for continued antimicrobial development. Pyrinezolid (PZ), a novel oxazolidinone compound, can effectively inhibit most gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Though PZ is a promising antimicrobial candidate, the druggability of PZ is limited by its poor water solubility. Therefore, the amphipathic mPEG-PLLA copolymer was used to prepare the pyrinezolid micelles (PZ-M). Herein, we described the preparation, pharmacokinetic properties, tissue distribution, efficacy and toxicity of PZ-M. In vivo studies show that PZ-M possess prolonged blood circulation time and increased oral bioavailability compared with free PZ. Meanwhile, PZ-M increase lung PZ exposure and reduce liver and kidney exposure, which indicates that PZ-M may enhance the efficacy in vivo in MRSA-related pneumonia patients and decrease potential renal and hepatic toxicities.

Diagnosis and surgical treatment of cervical macrocystic lymphatic malformations in infants.

The treatment of lymphatic malformations (LMs) represents a great clinical challenge. The present study reported on the treatment of 68 infants with cervical macrocystic LMs using surgical resection. The cases were retrospectively analyzed. All patients underwent pre-operative ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) examinations. The surgery was performed under general anesthesia with endotracheal intubation. Ultrasonograms showed that 24 cases were monolocular, 44 were multilocular, 16 had no echo, 20 had a uniform low-level echo and 32 had a non-uniform low-level echo. CT showed non-enhancing low-attenuating cystic lesions and attenuation values of 10-45 HU. The magnetic resonance images of the LMs showed a low signal intensity on T1-weighted imaging (WI) and a high signal intensity on T2-WI. Complete resection was achieved in 56 patients, subtotal resection in eight and partial resection in four. Two complications were noted, including reversible paresis of the marginal mandibular branch of the facial nerve and a surgical-site infection. One patient in whom partial resection was achieved had recurrence at ~2 months after the surgery. Ultrasonography, CT and MRI clearly demonstrated the size, shape, extent and adjacent structures of LMs, which aided in surgical planning and assessment of potential risks. Surgical excision increased the chances of cure and was relatively safe for infants aged <1 year. Location and extent, rather than age, were determined to be the most important factors for successful surgical treatment.

An autosomal dominant high bone mass phenotype in association with craniosynostosis in an extended family is caused by an LRP5 missense mutation.

Gain-of-function mutations in LRP5 have been shown to cause high BMD disorders showing variable expression of some clinical symptoms, including torus palatinus and neurological complications. In an extended family, we were able to add craniosynostosis and developmental delay to the clinical spectrum associated with LRP5 mutations. We report on an extended four-generation family with 13 affected individuals (7 men and 6 women) in which an autosomal dominant type of osteosclerosis segregates. Osteosclerosis was most pronounced in the cranial base and calvarium, starting in early childhood with variable expression and a progressive character. Craniosynostosis at an early age was reported in four affected family members (two males and two females). The patients also presented with dysmorphic features (macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones, prominent jaw). They have normal height and proportions. Neurological complications like entrapment of cranial nerves resulting in optical nerve atrophy, hearing loss, and facial palsy were reported in two individuals. A mild developmental delay was reported in three affected individuals. None of the patients have torus palatinus, increased rate of fractures, osteomyelitis, hepatosplenomegaly, or pancytopenia. A missense mutation 640G-->A (A214T) in the low-density lipoprotein receptor-related protein 5 (LRP5) gene was found in all affected individuals analyzed, including cases in whom craniosynostosis, a mild developmental delay, and/or macrocephaly is observed. To our knowledge, this is the first report in the literature of patients presenting with autosomal dominant osteosclerosis in whom a variable expression of craniosynostosis, macrocephaly, and mild developmental delay is observed, which is most likely associated with a mutation in the LRP5 gene. These phenotypes can therefore be added to the clinical spectrum of LRP5-associated bone disorders.

Enhanced antitumor effects by docetaxel/LL37-loaded thermosensitive hydrogel nanoparticles in peritoneal carcinomatosis of colorectal cancer.

Intraperitoneal chemotherapy was explored in clinical trials as a promising strategy to improve the therapeutic effects of chemotherapy. In this work, we developed a biodegradable and injectable drug-delivery system by coencapsulation of docetaxel (Doc) and LL37 peptide polymeric nanoparticles (Doc+LL37 NPs) in a thermosensitive hydrogel system for colorectal peritoneal carcinoma therapy. Firstly, polylactic acid (PLA)-Pluronic L35-PLA (PLA-L35-PLA) was explored to prepare the biodegradable Doc+LL37 NPs using a water-in-oil-in-water double-emulsion solvent-evaporation method. Then, biodegradable and injectable thermosensitive PLA-L64-PLA hydrogel with lower sol-gel transition temperature at around body temperature was also prepared. Transmission electron microscopy revealed that the Doc+LL37 NPs formed with the PLA-L35-PLA copolymer were spherical. Fourier-transform infrared spectra certified that Doc and LL37 were encapsulated successfully. X-ray diffraction diagrams indicated that Doc was encapsulated amorphously. Intraperitoneal administration of Doc+LL37 NPs-hydrogel significantly suppressed the growth of HCT116 peritoneal carcinomatosis in vivo and prolonged the survival of tumor-bearing mice. Our results suggested that Doc+LL37 NPs-hydrogel may have potential clinical applications.

[Effect of factors on callus biomass and synthetic mass of hypericin in Hypericum perforatum].

OBJECTIVE: To study the effect of several factors on the quantity of hypericin in H. perforatum callus. METHOD: High efficiency liquid phase chromatography and plant tissue culture were applied. RESULT AND CONCLUSION: When the ratio of nitro-nitrogen to amina-nitrogen is 3:1, the callus biomass is 1.6-fold and the synthetic mass of hypericin rises. 0.1-0.20 mg x L(-1) mannose improves the content of total hypericin. The addition of PVP or PVPP can promote improvement of the growth and biosynthesis of callus.