Optimization of a Decellularization/Recellularization Strategy for Transplantable Bioengineered Liver

The liver is a complex organ that requires constant perfusion for the delivery of nutrients and oxygen and the removal of waste in order to survive. Efforts to recreate or mimic the liver microstructure via a ground-up approach are essential for liver tissue engineering. A decellularization/recellularization strategy is one of the approaches aiming at the possibility of producing a fully functional organ with in vitro-developed construction for clinical applications to replace failed livers, such as end-stage liver disease (ESLD). However, the complexity of the liver microarchitecture along with the limited suitable hepatic component, such as the optimization of the extracellular matrix (ECM) of the biomaterials, the selection of the seed cells, and development of the liver-specific three-dimensional (3D) niche settings, pose numerous challenges. In this chapter, we have provided a comprehensive outlook on how the physiological, pathological, and spatiotemporal aspects of these drawbacks can be turned into the current challenges in the field, and put forward a few techniques with the potential to address these challenges, mainly focusing on a decellularization-based liver regeneration strategy. We hypothesize the primary concepts necessary for constructing tissue-engineered liver organs based on either an intact (from a naïve liver) or a partial (from a pretreated liver) structure via simulating the natural development and regenerative processes

Antioxidant Capacity and Proanthocyanidin Composition of the Bark of Metasequoia glyptostroboides

Metasequoia glyptostroboides Hu et Cheng is the only living species in the genus Metasequoia Miki ex Hu et Cheng (Taxodiaceae), which is well known as a “living fossil” species. In the Chinese folk medicine, the leaves and bark of M. glyptostroboides are used as antimicrobic, analgesic, and anti-inflammatory drug for dermatic diseases. This study is the first to report the free radical scavenging capacity, antioxidant activity, and proanthocyanidin composition of the bark of M. glyptostroboides. We observed total of six extracts and fractions, which were easily obtained by water-ethanol extraction and followed by a further separation with D101 resin column chromatography, had significant DPPH radical, superoxide anion radical, and hydroxyl radical scavenging capacity, total antioxidative capacity (T-AOC), lipid peroxidation inhibitory activity, and metal ions chelating capacity. The fraction MGEB, which was obtained by 60% ethanol extraction and followed by a further separation with D101 resin column chromatograph, possessed the highest proanthocyanidin content and the highest free radical scavenging and antioxidant activities. Furthermore, MGEB could significantly protect against CCl4 induced acute liver injury through inhibition of oxidative stress in mice. In addition, ten proanthocyanidins were isolated from MGEB, and six of them were firstly reported from this plant

Antitumor Activity of 2,9-Di-\u3cem\u3eSec\u3c/em\u3e-Butyl-1,10-Phenanthroline

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin

Applications of functional near-infrared spectroscopy in non-drug therapy of traditional Chinese medicine: a review

Non-drug therapies of traditional Chinese medicine (TCM), including acupuncture, massage, tai chi chuan, and Baduanjin, have emerged as widespread interventions for the treatment of various diseases in clinical practice. In recent years, preliminary studies on the mechanisms of non-drug therapies of TCM have been mostly based on functional near-infrared spectroscopy (fNIRS) technology. FNIRS is an innovative, non-invasive tool to monitor hemodynamic changes in the cerebral cortex. Our review included clinical research conducted over the last 10 years, establishing fNIRS as a reliable and stable neuroimaging technique. This review explores new applications of this technology in the field of neuroscience. First, we summarize the working principles of fNIRS. We then present preventive research on the use of fNIRS in healthy individuals and therapeutic research on patients undergoing non-drug therapies of TCM. Finally, we emphasize the potential for encouraging future advancements in fNIRS studies to establish a theoretical framework for research in related fields

Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study

Background and aimsReal-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population.MethodsA total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments.ResultsThrough 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P < 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P < 0.05).ConclusionThis real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower.Clinical trial registrationhttps://ClinicalTrials.gov, identifier NCT05453448

Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src

A prospective and randomized comparison of rigid ureteroscopic to flexible cystoscopic retrieval of ureteral stents

Abstract Background Flexible cystoscopy has become an accepted alternative for stent retrieval. However, it is associated with higher cost. Some reports have described experiences of using rigid ureteroscope to retrieve ureteral stents. We compared rigid ureteroscopic to flexible cystoscopic retrieval of ureteral stents in a prospective and randomized clinical trial. Methods Three hundred patients treated with ureteral stents between July 2012 and July 2013 were accrued in this study. These patients were divided into two groups using the random number table method. Group A, with 162 patients, had stents removed with a flexible cystoscope and Group B, with 138 patients, had stents removed with a rigid ureteroscope. All procedures were performed under topical anesthesia by the same urologist. Patients in each group were compared in terms of preoperative, perioperative, and postoperative data. Postoperative data were collected using telephone interview on the postoperative day two. The postoperative questionnaire used included three items: hematuria, irritable bladder symptoms, and pain scores. Results All the stents were retrieved successfully. No statistical differences were noted between the two groups in terms of gender, age, laterality and duration of the stents, operative time, postoperative hematuria, irritable bladder symptoms, and pain scores. The per-use cost of instrument was much higher for the flexible cystoscopic group, RMB 723.1 versus 214.3 (USD 107.9 versus 28.2), P < 0.05. Conclusion Ureteral stent retrieval using rigid ureteroscope under topical anesthesia is as safe and effective as flexible cystoscope but with a much lower cost to patients. Trial registration This study was registered with Chinese Clinical Trial Registry on March 27, 2017 (retrospective registration) with a trial registration number of ChiCTR-IOR-17010986