development-an-efficient-murine-tissue-expansion-model-for-skin

Development of an Efficient Murine Tissue Expansion Model for Skin Regeneration Research

Skin regeneration is essential for the healing of various superficial wounds and can be promoted by mechanical stimulation. Tissue expansion is a widely ...

Shanghai Jiaotong University School of Medicine

Tongji University School of Medicine

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for  autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice . Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation.

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

 The cervical or thoracic region is currently the main donor site for repair of facial multiunit defects (FMUDs); however, its extensive clinical utilization encompasses the need for flap prefabrication and microsurgical techniques.  To illuminate the feasibility of treating FMUD with expanded scalp flaps and laser depilation.  From 2016 to 2020, 17 patients with facial giant congenital melanocytic nevi (GCMN) underwent scalp expansion for FMUD reconstruction. A three-stage surgical treatment plan was attempted and laser depilation was scheduled during the expansion period and postrepair surgeries.  All the flaps survived successfully and were able to cover the entire facial defect. The average three-stage treatment time was 4.5 ± 1.3 months. The defect sites included the forehead, nose, cheek, temporal, and eye areas. The maximum defect area was 9 × 30 cm. The average number of laser treatments was 4.6 ± 2.9 times. The average treatment period was 26.8 months. Sixteen patients (94.1%) reported satisfactory outcome.  Expanded scalp flap combined with laser depilation is feasible for FMUD repair and warrants further investigation. Clinical Trail Registration Information: Translational Medicine Ethics Review Committee, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine (SH9H-2021-T144-3).

Reconstruction of Facial Multiunit Defects Using Expanded Scalp Flap with Laser Depilation in a Group of Predominantly Pediatric Patients.

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Tissue expansion for treating giant congenital melanocytic nevi (GCMN) is a commonly used surgical method. However, the procedure's efficacy is often hindered by anatomical and histologic characteristics and blood supply, particularly in the extremities and trunk. Enhancing expansion efficiency while reducing complications is thus a topic to be investigated, especially for pediatric patients undergoing rapid physical and psychological development with higher risks of noncompliance to medical instructions. The purpose of this study was to explore the effectiveness of expansion in extremities and trunk by immobilizing the acellular dermal matrix (ADM) in the gravitational force zone of inflating expanders.

Acellular Dermal Matrix-Assisted Tissue Expansion for Giant Congenital Melanocytic Nevi of the Extremities and Trunk in Pediatric Patients.

The reconstruction of large-sized soft tissue defects remains a substantial clinical challenge, with adipose tissue engineering emerging as a promising solution. The acellular dermal matrix (ADM), known for its intricate spatial arrangement and active cytokine involvement, is widely employed as a scaffold in soft tissue engineering. Since ADM shares high similarity with decellularized adipose matrix, it holds potential as a substitute for adipose tissue. This study explores the adipogenic ability of a spongy material derived from ADM via vacuum-thermal crosslinking (T-ADM), characterized by high porosity, adjustable thickness, and suitable mechanical strength. Adipose-derived stem cells (ADSCs) are considered ideal seed cells in adipose tissue engineering. Nevertheless, whether pre-adipogenic induction is necessary before their incorporation remains debatable. In this context, ADSCs, both with and without pre-adipogenic induction, were seeded into T-ADM to regenerate vascularized adipose tissue. A comparative analysis of the two constructs was performed to evaluate angiogenesis and adipogenesis, and tissue regeneration efficacy. Additionally, RNA-seq analysis was utilized to investigate the potential mechanisms. The results showed that T-ADM exhibited good performance in terms of volume retention and maintenance of adipocyte phenotype, confirming its suitability as a scaffold for adipose tissue engineering.outcomes demonstrated that pre-adipogenic induction enhanced the adipogenic level of ADSCs, but reduced their ability to promote vascularization. Furthermore, constructs utilizing pre-induced ADSCs showed an insignificant superiority infat formation, and neovascularization compared with those with non-induced ADSCs, which may be attributed to similar macrophage regulation, and balanced modulation of the proliferator-activated receptor-and hypoxia-inducible factor 1pathways. Consequently, the direct use of ADSCs is advocated to streamline the engineering process and reduce associated costs. The combined strategy of T-ADM with ADSCs proves to be feasible, convenient and effective, offering substantial potential for addressing large-sized tissue deficits and facilitating clinical applications.

Thermal-crosslinked acellular dermal matrix combined with adipose-derived stem cells to regenerate vascularized adipose tissue.

Defects in the posterior lamella of the eyelid are prevalent in the clinical settings, which comprises the tarsal plate and conjunctiva and has limited regenerative capacity. Currently, homogenous scaffolds are used for repair, but they fail to recapitulate the natural bilayer structure and reepithelialization. In this study, we designed a bilamellar scaffold (bGA-ADM) with a heterogeneous structure to repair such defects and promote the integrated regeneration of tarso-conjunctival composite tissue.

Article	Year
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy\| PubMed ID: 33634751	2021
RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation. Aging\| PubMed ID: 34496349	2021
Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition). Military Medical Research\| PubMed ID: 35361280	2022
Reconstruction of Facial Multiunit Defects Using Expanded Scalp Flap with Laser Depilation in a Group of Predominantly Pediatric Patients. Facial plastic surgery & aesthetic medicine\| PubMed ID: 35687387	2022
Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition). Military Medical Research\| PubMed ID: 35978389	2022
Acellular Dermal Matrix-Assisted Tissue Expansion for Giant Congenital Melanocytic Nevi of the Extremities and Trunk in Pediatric Patients. Plastic and reconstructive surgery\| PubMed ID: 38546404	2025
Thermal-crosslinked acellular dermal matrix combined with adipose-derived stem cells to regenerate vascularized adipose tissue. Biomedical materials (Bristol, England)\| PubMed ID: 39879651	2025
Heterogeneous-structural bilamellar bionic scaffold for integrated regeneration of tarso-conjunctival composite tissue. Journal of translational medicine\| PubMed ID: 41715185	2026

Xing Huang

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