HER2-specific liposomes loaded with proteinaceous BRET pair as a promising tool for targeted self-excited photodynamic therapy.

Photodynamic therapy (PDT) for deep-seated tumors is still challenging due to the limited penetration of visible light through tissues. To resolve this limitation, systems based on bioluminescence resonance energy transfer (BRET), that do not require an external light source are proposed. Herein, for BRET-activated PDT we developed proteinaceous BRET-pair consisting of luciferase NanoLuc, which acts as energy donor upon addition of luciferase specific substrate furimazine, and phototoxic protein SOPP3 as a photosensitizer. We have shown that hybrid protein NanoLuc-SOPP3 is an excellent BRET pair with BRET ratio of 1.12. Targeted delivery of NanoLuc-SOPP3 BRET pair via tumor-specific small liposomes (∼100 nm) to tumors overexpressing the HER2-receptor (human epidermal growth factor receptor 2) was demonstrated in vitro and in vivo. The proposed BRET-activated system has been shown to significantly suppress tumor growth in a model of subcutaneous and, more importantly, deep-seated tumor model. Taking into account the in vivo efficiency of proposed BRET-activated system, we believe that it has great potential for depth-independent PDT and can significantly broaden the application of PDT in the clinic.

Shatavari Supplementation in Postmenopausal Women Improves Handgrip Strength and Increases Vastus lateralis Myosin Regulatory Light Chain Phosphorylation but Does Not Alter Markers of Bone Turnover.

Shatavari has long been used as an Ayurvedic herb for women's health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double-blind trial, 20 postmenopausal women (68.5 ± 6 years) ingested either placebo (N = 10) or shatavari (N = 10; 1000 mg/d, equivalent to 26,500 mg/d fresh weight shatavari) for 6 weeks. Handgrip and knee extensor strength were measured at baseline and at 6 weeks. Vastus lateralis (VL) biopsy samples were obtained. Data are presented as difference scores (Week 6-baseline, median ± interquartile range). Handgrip (but not knee extensor) strength was improved by shatavari supplementation (shatavari +0.7 ± 1.1 kg, placebo -0.4 ± 1.3 kg; p = 0.04). Myosin regulatory light chain phosphorylation, a known marker of improved myosin contractile function, was increased in VL following shatavari supplementation (immunoblotting; placebo -0.08 ± 0.5 a.u., shatavari +0.3 ± 1 arbitrary units (a.u.); p = 0.03). Shatavari increased the phosphorylation of Aktser473 (Aktser473 (placebo -0.6 ± 0.6 a.u., shatavari +0.2 ± 1.3 a.u.; p = 0.03) in VL. Shatavari supplementation did not alter plasma markers of bone turnover (P1NP, ß-CTX) and stimulation of human osteoblasts with pooled sera (N = 8 per condition) from placebo and shatavari supplementation conditions did not alter cytokine or metabolic markers of osteoblast activity. Shatavari may improve muscle function and contractility via myosin conformational change and further investigation of its utility in conserving and enhancing musculoskeletal function, in larger and more diverse cohorts, is warranted.

Review of Analytical Methods and Reporting of the Polyphenol Content of Tart Cherry Supplements in Human Supplementation Studies Investigating Health and Exercise Performance Effects: Recommendations for Good Practice.

Tart cherries (TC) are a rich source of polyphenols that elicit antioxidant and anti-inflammatory effects. As a consequence, the effects of TC derived supplements on markers of human health, exercise performance and sleep have been investigated. Supplementation protocols have been highly variable across studies and the dose of bioactive compounds used has often been poorly characterized. Specific and non-specific analytical methods were employed for measuring the total polyphenol and anthocyanin content in TC supplements. This review critically analyses the supplementation protocols and the analytical methods used for the characterization of TC supplements, culminating in recommendations for good practice in the analysis and reporting of the polyphenol content and profile of TC products. A literature search was conducted using PubMed/Medline and Web of Science up to May 4th, 2020, including studies published in all years prior. Only articles written in English that provided a TC dietary supplement as opposed to fresh whole TC were included in this review. Forty-three studies were identified as eligible and included for analysis in this review. The studies investigated the effects of TC supplementation on various aspects of human health, exercise recovery and performance and sleep. Twenty studies conducted an analysis of TC supplement and reported total polyphenol/anthocyanin content. Six studies did not report the polyphenol content of the TC supplement used. Seventeen studies reported the TC supplement polyphenol content but this was derived from previously published studies and presumably different supplement batches. The duration of the supplementation protocol ranged from acute supplementation to 84 days, meanwhile the total polyphenol and anthocyanin dose ranged from 143 to 2,140 mg/day and 15 to 547 mg/day, respectively. Due to the variety of specific and non-specific analytical methods used, the relative efficacy of different doses and polyphenol blends cannot reliably be extrapolated from critical analysis of the literature. Future studies should conduct an analysis of the study supplement batch. In addition to analysis and reporting of total polyphenol content, specific analytical methods such as HPLC UV/MS should be used to quantify total and individual anthocyanin contents.

Cannabidiol - therapeutic and legal aspects.

Cannabidiol (CBD) is an alkaloid present in Cannabis sativa, along with tetrahydrocannabinol (THC) and more than 100 other substances belonging to a group of compounds called cannabinoids. Whereas the legal status and medical use of Cannabis is a controversial issue in many countries, inconsistent legislation makes CBD status even more complicated. Some CBD products are legal in some countries, while banned in other countries, further compounding the confusion. In 2018, the Food and Drug Administration (FDA) approved the first CBD containing medical product, Epidiolex®, for the treatment of paediatric seizures. Currently, several clinical trials are in progress for the potential treatment of neurologic and behavioural disorders. CBD's current legal and regulatory status is a continuously evolving issue; the current review is presenting historical and present information regarding the use of CBD products worldwide.

A combined laparoscopic and endoscopic approach for the removal of a gastric foreign body. A case report and review of the literature.

BACKGROUND AND AIM: Foreign bodies that are ingested and will not pass spontaneously through the gastrointestinal tract, need to be removed either endoscopically or surgically. Surgery will be required when endoscopy alone fails to retrieve the foreign body. In this study, we aimed to present our experience with an combined minimal invasive approach for the removal of a gastric foreign body and to review the medical literature on the complexities related to its management. METHODS: We report a successful technique represented by a combined laparoscopic and endoscopic approach for the retrieval of a gastric foreign body. A 51 year old male patient, with a longstanding psychiatric history, who ingested a folded bank card with suicidal purpose, had the foreign body removed using this combined minimal invasive approach. RESULTS: The operating time was 150 minutes, there was no blood loss and no perioperative complications. The patient fulfilled the discharge criteria on the 3rd postoperative day DISCUSSION : The approach for ingested foreign bodies should be considered for each patient independently, depending on the characteristics, location and existence of complications of the retained object. CONCLUSION: This combined minimal invasive technique is safe and feasible, with excellent results for the retrieval of large, non-malleable gastric foreign bodies. KEY WORDS: Endoscopy, Foreign body, Laparoscopy, Removal.

Complex malformation of the inferior vena cava.

Malformations of the inferior vena cava (IVC) are rare presentations, exceptional in children, and are usually asymptomatic.They are caused by disturbances in the embryological formation of the venous system or can develop as a result of perinatal venous thrombosis with secondary impairment of the venous development. We report the case of a 14 year old boy,admitted for pediatric evaluation before undergoing plastic surgery in order to remove superficial varicose veins of the lower abdomen. The patient presents with inequality in circumference and length of the legs. Laboratory investigations are normal and the abdominal ultrasound describes hypoplasia of the retrohepatic segment of the inferior vena cava. The diagnosis of complex malformation of the abdominal deep venous system (retrohepatic vena cava atresia, cavo-caval anastomosis through azygos veins, abnormal formation of the inferior vena cava with the absence of the left iliac vein) was established through a CT angiography. The presence of abdominal varicose dilations should indicate the necessity to closely look for malformations of the portal and/or caval venous systems.

The general phase behavior of mixtures of 1-alkyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]amide ionic liquids with n-alkyl alcohols.

The liquid-liquid equilibrium (LLE) phase behavior of mixtures of 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]amide (C(2)mimNTf(2)) with the n-alkyl alcohols (C(n)OH; 3≤n≤8) is described. By applying the cloud-point method, the LLEs were determined over a temperature range of 275-423 K at ambient pressure. Partial miscibility with upper critical solution temperatures (UCST) was observed. The UCST increase with increasing chain length of the alcohols. The phase diagrams were analyzed numerically by presuming Ising criticality. Concepts for the description of the asymmetry of the phase diagram by presuming the validity of the rectilinear diameter rule or a nonlinear diameter requested by the theory of complete scaling were applied. The results (UCST, critical composition, width and diameter of the phase diagrams) are compared with similar systems and discussed in terms of the corresponding state behavior; they map on a single curve. From at least 45 individual phase diagrams, general aspects of the behavior of this ionic liquid-alcohol mixture type were extracted. A simple empirical relationship was formulated to allow the description of the UCST with an accuracy of about 10 K when taking the ratio of the molar volumes of the alcohol and the 1-alkyl-3-methylimidazolium cation of the ionic liquid into account.

Nanoscale strain-induced pair suppression as a vortex-pinning mechanism in high-temperature superconductors.

Boosting large-scale superconductor applications require nanostructured conductors with artificial pinning centres immobilizing quantized vortices at high temperature and magnetic fields. Here we demonstrate a highly effective mechanism of artificial pinning centres in solution-derived high-temperature superconductor nanocomposites through generation of nanostrained regions where Cooper pair formation is suppressed. The nanostrained regions identified from transmission electron microscopy devise a very high concentration of partial dislocations associated with intergrowths generated between the randomly oriented nanodots and the epitaxial YBa(2)Cu(3)O(7) matrix. Consequently, an outstanding vortex-pinning enhancement correlated to the nanostrain is demonstrated for four types of randomly oriented nanodot, and a unique evolution towards an isotropic vortex-pinning behaviour, even in the effective anisotropy, is achieved as the nanostrain turns isotropic. We suggest a new vortex-pinning mechanism based on the bond-contraction pairing model, where pair formation is quenched under tensile strain, forming new and effective core-pinning regions.

Utilization of an Hg(2+)-sensitive membrane-electrode in the complexometric determination of Bi(3+), Fe(3+) and Cr(3+).

The paper reports the results obtained in the complexometric determination of Bi(3+), Fe(3+) and Cr(3+) by using an Hg(2+)-sensitive membrane-electrode for the end-point indication. The determination of Bi(3+) and Fe(3+) is performed after addition of mercuric complexonate from which these cations release Hg(2+) by means of which the electrode senses the equivalence point. In the case of Cr(3+) an excess of complexone is added and the surplus is titrated with a standard solution of Hg(2+) in the presence of the Hg(2+)-sensitive membrane-electrode.