In recent years, bone tissue engineering (BTE), as a multidisciplinary field, has shown considerable promise in replacing traditional treatment modalities (i.e., autografts, allografts, and ...xenografts). Since bone is such a complex and dynamic structure, the construction of bone tissue composite materials has become an attractive strategy to guide bone growth and regeneration. Chitosan and its derivatives have been promising vehicles for BTE owing to their unique physical and chemical properties. With intrinsic physicochemical characteristics and closeness to the extracellular matrix of bones, chitosan-based composite scaffolds have been proved to be a promising candidate for providing successful bone regeneration and defect repair capacity. Advances in chitosan-based scaffolds for BTE have produced efficient and efficacious bio-properties via material structural design and different modifications. Efforts have been put into the modification of chitosan to overcome its limitations, including insolubility in water, faster depolymerization in the body, and blood incompatibility. Herein, we discuss the various modification methods of chitosan that expand its fields of application, which would pave the way for future applied research in biomedical innovation and regenerative medicine.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Estrogen therapy is widely used as a supplementary treatment after hysteroscopy for female infertility patients owing to its protective function that improves endometrial regeneration and ...menstruation, inhibits recurrent adhesions, and improves subsequent conception rate. The endometrial protective function of such estrogen administration pre-surgery is still controversial. In the current study, 12 infertility patients were enrolled, who were treated with estrogen before hysteroscopy surgery. Using cutting-edge metabolomic analysis, we observed alterations in the pentose phosphate pathway (PPP) intermediates of the patient's endometrial tissues. Furthermore, using Ishikawa endometrial cells, we validated our clinical discovery and identified estrogen-ESR-G6PD-PPP axial function, which promotes estrogen-induced cell proliferation.
Titanium (Ti) and molybdenum (Mo) were added simultaneously to improve the strength and toughness of medium-carbon martensitic steel. The influences of tempering temperatures on the microstructure, ...strength, and toughness of the as-developed martensitic steel were investigated. The microstructure of Ti–Mo-bearing martensitic steel consisted of martensite without apparent recovery and fine precipitates at the optimal tempering temperature of 200 °C, and the tensile strength of 1700 MPa and − 40 °C impact energy of 43 J were simultaneously realized. With increasing tempering temperature, carbides were transformed from
ε
-carbides to (Ti, Mo)C and Fe
3
C particles. Moreover, both the content and size of precipitates increased with increasing tempering temperature. The decreased impact energy of the quenching-tempering steel tempered at 650 °C could be ascribed to the increased coarsening of (Ti, Mo)C and Fe
3
C particles. In addition, (Ti, Mo)C particles mainly precipitated on Fe
3
C particles and at dislocations.
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years of age, accompanied by an elevation of follicle‐stimulating hormone. Though POI affects many aspects of ...women's health, its major causes remain unknown. Many clinical studies have shown that POI patients are generally underweight, indicating a potential correlation between POI and metabolic disorders. To understand the pathogenesis of POI, we performed metabolomics analysis on serum and identified branch‐chain amino acid (BCAA) insufficiency‐related metabolic disorders in two independent cohorts from two clinics. A low BCAA diet phenotypically reproduced the metabolic, endocrine, ovarian, and reproductive changes of POI in young C57BL/6J mice. A mechanism study revealed that the BCAA insufficiency‐induced POI is associated with abnormal activation of the ceramide‐reactive oxygen species (ROS) axis and consequent impairment of ovarian granulosa cell function. Significantly, the dietary supplement of BCAA prevented the development of ROS‐induced POI in female mice. The results of this pathogenic study will lead to the development of specific therapies for POI.
Synopsis
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years. The current study identified that POI is related to metabolic disorders in these patients.
Serum metabolomic analysis reveals a branch chain amino acid (BCAA) insufficiency‐related metabolic disorder in two independent cohorts of POI patients.
BCAA insufficiency leads to POI via the upregulation of ceramide.
Ceramide‐induced elevation of ROS contributes to the development of POI.
BCAA supplement protects the ovaries from POI in mice.
Premature ovarian insufficiency (POI) is a disease featured by early menopause before 40 years. The current study identified that POI is related to metabolic disorders in these patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Methods
We collected the clinical data of 260 patients admitted to the hospital from April 2003 to September 2019 with pathologically confirmed intravenous leiomyomatosis (IVL) and followed up with ...these patients regularly. Univariate and multivariate logistic regression analyses were carried out on the relevant recurrence factors.
Results
A total of 166 patients were regularly followed up, the median follow‐up time was 36 (range 2–168) months, 14 (5.4%) patients eventually relapsed, and the median recurrence time was 8.5 (range 2–42) months. The univariate analysis showed that age (p = 0.003) and surgical type (p < 0.001) were associated with recurrence, and multivariate regression analysis demonstrated that surgical type was the only factor associated with recurrence (p < 0.001, OR 20.01).
Conclusions
The use of gonadotrophin releasing hormone agonist (GnRHa) cannot reduce the postsurgical recurrence rate of patients with UIVL. Compared to total hysterectomy and bilateral salpingo‐oophorectomy (TH‐BSO), total hysterectomy (TH) does not increase the odds of recurrence, but the chance of recurrence with tumorectomy (TE) is 20 times higher than that of TH‐BSO.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Platelet-rich fibrin, a classical autologous-derived bioactive material, consists of a fibrin scaffold and its internal loading of growth factors, platelets, and leukocytes, with the gradual ...degradation of the fibrin scaffold and the slow release of physiological doses of growth factors. PRF promotes vascular regeneration, promotes the proliferation and migration of osteoblast-related cells such as mesenchymal cells, osteoblasts, and osteoclasts while having certain immunomodulatory and anti-bacterial effects. PRF has excellent osteogenic potential and has been widely used in the field of bone tissue engineering and dentistry. However, there are still some limitations of PRF, and the improvement of its biological properties is one of the most important issues to be solved. Therefore, it is often combined with bone tissue engineering scaffolds to enhance its mechanical properties and delay its degradation. In this paper, we present a systematic review of the development of platelet-rich derivatives, the structure and biological properties of PRF, osteogenic mechanisms, applications, and optimization to broaden their clinical applications and provide guidance for their clinical translation.
Components in blood play an important role in wound healing and subsequent tissue regeneration processes. The fibrin matrix and various bioactive molecules work together to participate in this ...complex yet vital biological process. As a means of personalized medicine, autologous platelet concentrates have become an integral part of various tissue regeneration strategies. Here, we focus on how autologous platelet concentrates play a role in each stage of tissue healing, as well as how they work in conjunction with different types of biomaterials to participate in this process. In particular, we highlight the use of various biomaterials to protect, deliver and enhance these libraries of biomolecules, thereby overcoming the inherent disadvantages of autologous platelet concentrates and enabling them to function better in tissue regeneration.
ADP Ribosylation Factor 6 (ARF6) is a part of the RAS superfamily and regulates vesicular trafficking, remodeling of membrane lipids, and signaling pathways. Our previous study has found that ARF6, ...functioned as a downstream of Kras/ERK signaling pathway, could promote proliferation and Warburg effect in pancreatic cancer cells. Moreover, ARF6 is promising to be a biomarker for predicting prognosis of pancreatic cancer. Ferroptosis is a new defined iron-dependent form of nonapoptotic cell death, which is closely related to Kras mutation. Therefore, it is urgent to further explore the relationship between ARF6 and ferroptosis. Our study demonstrated that ARF6 did not directly regulate lipid peroxidation, but endowed pancreatic cancer cells to a status that is sensitive to oxidative stress, especially RSL3-induced lipid peroxidation. Further study revealed that ARF6 could also regulate gemcitabine resistance via multiple pathways. In conclusion, ARF6 has a profound effect on pancreatic cancer development.
mRNA‐mediated protein replacement represents a promising concept for the treatment of liver disorders. Children born with fumarylacetoacetate hydrolase (FAH) mutations suffer from Hepatorenal ...Tyrosinemia Type 1 (HT‐1) resulting in renal dysfunction, liver failure, neurological impairments, and cancer. Protein replacement therapy using FAH mRNA offers tremendous potential to cure HT‐1, but is currently hindered by the development of effective mRNA carriers that can function in diseased livers. Structure‐guided, rational optimization of 5A2‐SC8 mRNA‐loaded dendrimer lipid nanoparticles (mDLNPs) increases delivery potency of FAH mRNA, resulting in functional FAH protein and sustained normalization of body weight and liver function in FAH−/− knockout mice. Optimization using luciferase mRNA produces DLNP carriers that are efficacious at mRNA doses as low as 0.05 mg kg−1 in vivo. mDLNPs transfect > 44% of all hepatocytes in the liver, yield high FAH protein levels (0.5 mg kg−1 mRNA), and are well tolerated in a knockout mouse model with compromised liver function. Genetically engineered FAH−/− mice treated with FAH mRNA mDLNPs have statistically equivalent levels of TBIL, ALT, and AST compared to wild type C57BL/6 mice and maintain normal weight throughout the month‐long course of treatment. This study provides a framework for the rational optimization of LNPs to improve delivery of mRNA broadly and introduces a specific and viable DLNP carrier with translational potential to treat genetic diseases of the liver.
Structure‐guided, rational optimization of mRNA‐loaded dendrimer lipid nanoparticles (mDLNPs) is conducted to improve mRNA delivery efficacy for therapeutic application. Delivery of luciferase mRNA by mDLNPs in vivo produces 107 photons s−1 luminescence at 0.1 mg kg−1. In a difficult‐to‐treat Hepatorenal Tyrosinemia Type I (HT‐1) mouse model, mDLNPs effectively deliver fumarylacetoacetate hydrolase (FAH) mRNA that normalizes liver function and significantly extends survival.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The liver is organized into zones in which hepatocytes express different metabolic enzymes. The cells most responsible for liver repopulation and regeneration remain undefined, because fate mapping ...has only been performed on a few hepatocyte subsets. Here, 14 murine fate-mapping strains were used to systematically compare distinct subsets of hepatocytes. During homeostasis, cells from both periportal zone 1 and pericentral zone 3 contracted in number, whereas cells from midlobular zone 2 expanded in number. Cells within zone 2, which are sheltered from common injuries, also contributed to regeneration after pericentral and periportal injuries. Repopulation from zone 2 was driven by the insulin-like growth factor binding protein 2-mechanistic target of rapamycin-cyclin D1 (IGFBP2-mTOR-CCND1) axis. Therefore, different regions of the lobule exhibit differences in their contribution to hepatocyte turnover, and zone 2 is an important source of new hepatocytes during homeostasis and regeneration.
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