Induction of endometrial mesenchymal stem cells into tissue-forming cells suitable for fascial repair

Pelvic organ prolapse is a major hidden burden affecting almost one in four women. It is treated by reconstructive surgery, often augmented with synthetic mesh. To overcome the growing concerns of using current synthetic meshes coupled with the high risk of reoperation, a tissue engineering strategy has been developed, adopting a novel source of mesenchymal stem cells. These cells are derived from the highly regenerative endometrial lining of the uterus (eMSCs) and will be delivered in vivo using a new gelatin-coated polyamide scaffold. In this study, gelatin properties were optimized by altering the gelatin concentration and extent of crosslinking to produce the desired gelation and degradation rate in culture. Following cell seeding of uncoated polyamide (PA) and gelatin-coated meshes (PA + G), the growth rate of eMSCs on the PA + G scaffolds was more than that on the PA alone, without compromising cell shape. eMSCs cultured on the PA + G scaffold retained their phenotype, as demonstrated by W5C5/SUSD2 (eMSC-specific marker) immunocytochemistry. Additionally, eMSCs were induced to differentiate into smooth muscle cells (SMC), as shown by immunofluorescence for smooth muscle protein 22 and smooth muscle myosin heavy chain. eMSCs also differentiated into fibroblast-like cells when treated with connective tissue growth factor with enhanced detection of Tenascin-C and collagen type I as well as new tissue formation, as seen by Masson’s trichrome. In summary, it was demonstrated that the PA + G scaffold is an appropriate platform for eMSC delivery, proliferation and differentiation into SMC and fibroblasts, with good biocompatibility and the capacity to regenerate neo-tissue.     

The release of diazepam from poly(hydroxybutyrate-hydroxyvalerate) microspheres

Microspheres based on a poly(hydroxybutyrate-hydroxyvalerate) copolymer (PHBV) (Mw = 630 kD, 21% mol HV) were loaded with diazepam using different emulsion-solvent evaporation processes. Gelatin was used as a strategy to alter the release profile of the incorporated drug. The mean diameter of microspheres was from 30-40 micron. Drug-release from the microspheres over a 30-day period showed a characteristic triphasic release pattern with an initial burst effect, but was linear over the same period and without a burst effect when gelatin was used as a coating agent. Scanning electron microscopy revealed that the microspheres had different structures depending upon their method of preparation.     

Marine sponge-associated bacteria as a potential source for polyhydroxyalkanoates

Marine sponges are filter feeding porous animals and usually harbor a remarkable array of microorganisms in their mesohyl tissues as transient and resident endosymbionts. The marine sponge-microbial interactions are highly complex and, in some cases, the relationships are thought to be truly symbiotic or mutualistic rather than temporary associations resulting from sponge filter-feeding activity. The marine sponge-associated bacteria are fascinating source for various biomolecules that are of potential interest to several biotechnological industries. In recent times, a particular attention has been devoted to bacterial biopolymer (polyesters) such as intracellular polyhydroxyalkanoates (PHAs) produced by sponge-associated bacteria. Bacterial PHAs act as an internal reserve for carbon and energy and also are a tremendous alternative for fossil fuel-based polymers mainly due to their eco-friendliness. In addition, PHAs are produced when the microorganisms are under stressful conditions and this biopolymer synthesis might be exhibited as one of the survival mechanisms of sponge-associated or endosymbiotic bacteria which exist in a highly competitive and stressful sponge-mesohyl microenvironment. In this review, we have emphasized the industrial prospects of marine bacteria for the commercial production of PHAs and special importance has been given to marine sponge-associated bacteria as a potential resource for PHAs.     

羟丙基淀粉空心胶囊对螺内酯含量的影响

摘 要 目的： 考察羟丙基淀粉胶囊对螺内酯胶囊主药含量的影响。方法: 分别在强光（4 000 Lx±500 Lx）、高温（40℃）、高湿（相对湿度75%±5%）的条件下放置5 d和10 d,采用高效液相色谱法检查样品放置前后含量改变,同时观察外观、色泽等药物性状的变化。结果:经高温、高湿、光照试验后,测得标示含量值均在93.45%～100.37%之间,符合标准规定（93.0%～107.0%）。结论: 羟丙基淀粉空心胶囊与螺内酯相容性较好。     

Hypertension in a patient with medullary sponge kidney: A case report

Rationale:Medullary sponge kidney (MSK) is a congenital renal disorder characterized by recurrent nephrolithiasis or nephrocalcinosis. Recently, it has been found that MSK can be also combined with other diseases, such as primary aldosteronism and Beckwith-Wiedemann, but whether it is associated with secondary hypertension remains unknown.Patient concerns:A 22-year-old hypertensive female presented to our hospital characterized by hypokalemia and hypertension.Diagnosis:The laboratory examination showed secondary aldosteronism. And the common causes for secondary aldosteronism include renal artery stenosis, glomerulonephritis, lupus nephropathy, and diabetic nephropathy, all of which were excluded except MSK.Interventions:She was treated with angiotensin-converting enzyme inhibitors.Outcomes:Her blood pressure, serum potassium, and plasma renin levels were reversed after treatment with angiotensin-converting enzyme inhibitors.Lessons:We presumed that MSK may be associated with secondary hypertension, and the mechanism may be the activation of the renin-angiotensin-aldosterone system.     

腰椎板开窗术后微小骨粒回植模型的建立及意义

目的 建立兔腰椎板开窗术后微小骨粒回植模型,为临床提供实验依据。方法 将18只雄性新西兰兔,分为两组。对照组在全麻后以L5棘突为中心,充分显露左侧L5椎板,用微型小枪钳慢慢咬去椎板、黄韧带,进行开窗术,暴露约0.8 x 0.3 cm大小骨窗后直接缝合处理。实验组在L5左侧开窗后将开窗咬下的碎骨粒剪碎,然后将碎骨粒镶嵌于医用胶原蛋白海绵,塑成拱桥形,放置于硬膜外开窗处,缝合切口,术后观察椎板开窗位置CT及组织学变化。结果 CT检查示术后8周实验组开窗处微小骨粒形成菲薄的骨板,12周后形成的骨板较厚,骨梁连续,椎管形态及容积无明显变化,未见脊髓受压。对照组开窗处在8、12周局部有少量骨质增生,周围黏连组织侵入椎管,椎管未重建。结论 兔椎板开窗处再植自体微小骨粒的骨重建,形成的骨板可遮挡疤痕侵入椎管,减少椎管内黏连。     

Polymer-coated gelatin capsules as oral delivery devices and their gastrointestinal tract behaviour in humans

In oral delivery of protein and peptide drugs there is a great need for suitable devices for delivering the therapeutic agent-incorporated microspheres selectively in the intestine. It is essential that the drug-loaded multiple unit carrier system should be protected from the harsh environment of the stomach and deliver the carrier system in the large intestine where drug action or absorption is desired. Gelatin capsules were coated with various concentrations of sodium alginate and cross-linked with appropiate concentrations of calcium chloride and tested in vitro for resistance to gastric and intestinal medium. Gelatin capsules coated with 20% w/v of the polymer which gave the most promising result in vitro were evaluated in human volunteers for their in vivo gastro intestinal tract behaviour. The radiographical studies show that while the uncoated gelatin capsules disintegrated in the stomach within 15 min of ingestion, the alginate coated gelatin capsules remained intact as long as they were retained in the stomach (up to 3 h) and then migrated to the ileocecal region of the intestine and disintegrated.     

Vascularization into a porous sponge by sustained release of basic fibroblast growth factor

Vascularization into a poly(vinyl alcohol) (PVA) sponge was investigated using basic fibroblast growth factor (bFGF). This growth factor was impregnated into biodegradable gelatin microspheres for its sustained release and then the bFGF-containing microspheres or free bFGF were incorporated into PVA sponges. Following subcutaneous implantation into the back of mice, the bFGF-containing gelatin microspheres induced vascularization in and around the sponge to a significantly greater extent than that of free bFGF from 3 days after implantation. Significant ingrowth of fibrous tissue into the sponge was also observed when bFGF-containing microspheres were added to the sponge in contrast to free bFGF. Tissue ingrowth occurred into the deeper portion of the sponge over time while it accompanied formation of new capillaries. Empty gelatin microspheres had no effect on vascularization and the level of fibrous tissue ingrowth into the sponge was similar to that of the control group. It was concluded that incorporation of gelatin microspheres containing bFGF into the PVA sponge was effective in prevascularization of the sponge pores.     

Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles

PurposeCisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics.Methods and resultsHere, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6 ± 9.6 nm and 140.5 ± 10.9 nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P < 0.05) decrease in IC₅₀ value (8.3 μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1 μM) and cisplatin solution (40.2 μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54 ± 7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P < 0.05) greater than 51.68 ± 9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs.ConclusionTherefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.