Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche.

BACKGROUND: Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing. Previous studies have indicated that antler reserve mesenchyme (RM) cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages. AIM: To develop hydrogels from the antler RM matrix (HARM) and evaluate the effect on wound healing. METHODS: We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin. Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application. RESULTS: The results showed that HARM accelerated wound healing rate and reduced scar formation. Also, HARM stimulated the regeneration of cutaneous appendages and blood vessels, and reduced collagen fiber aggregation. Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site. The levels of fetal wound healing-related genes, including Collagen III and TGFß3 treated with HARM were all increased, while the expression levels of Collagen I, TGFß1, and Engrailed 1 were decreased in the healing. Moreover, the number of stem cells was increased in the fetal-like niche created by HARM, which may contribute to the regeneration of cutaneous appendages. CONCLUSION: Overall, we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds. We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing, and thus pave the way for HARM to be developed for the clinic use.

Genome-wide analysis of Chinese keloid patients identifies novel causative genes.

Background: Keloids are benign skin tumors that appears on skin lesions in humans. Keloids are characterized by invasive tumor growth and are highly prone to recurrence after treatment. The incidence of keloids is ethnically specific; however, the molecular mechanism underlying the incidence of keloids in the Chinese population remains unclear. To date, no reports appear to have been published on the molecular characteristics underlying keloids in the Chinese population from the perspective of whole-genome sequencing. Methods: In this study, we collected keloid samples from 9 keloid patients underwent surgery in the Department of Dermatology, The First Affiliated Hospital of Soochow University, paired them to normal skin tissues, and performed whole-exome sequencing. The average depth of the samples was 1,200×, and the average exome coverage was 98.90%. Results: The bioinformatics analysis identified 3,125 single nucleotide variants (SNVs) and 299 insertions/deletions (InDels). The major mutation characteristics of the SNVs were C > A and C > T. The non-synonymous SNV types included stopgain, and stoploss. The non-synonym InDels included frameshift deletion, frameshift insertion, and stopgain. We also found a total of 67,873 copy number variations (CNVs) in the samples. The genes with the highest mutation frequency included mucin 4 (MUC4) (55.6%), tubulin tyrosine ligase like 12 (TTLL12) (33.3%), calcium voltage-gated channel subunit alpha1 (CACNA1C) (33.3%), and mucin 12 (MUC12) (33.3%). The average tumor mutation burden (TMB) was 289 mutations/million base pair (MB). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mutated genes were mainly concentrated in micro ribonucleic acids in cancer and the calcium signaling pathway. The Gene Ontology (GO) analysis showed that mutant genes were mainly concentrated in binding cells, cell parts, and cellular processes. Conclusions: Whole-exome sequencing was performed in the Chinese keloid patients and some potential candidate genes related to keloid occurrence and development were identified, which may provide new molecular targets for the clinical diagnosis and treatment of keloid patients.

The ctDNA-based postoperative molecular residual disease status in different subtypes of early-stage breast cancer.

Background: Breast cancer is a highly heterogeneous disease. Early-stage, non-metastatic breast cancer is considered curable after definitive treatment. Early detection of tumor recurrence and metastasis through sensitive biomarkers is helpful for guiding clinical decision-making and early intervention in second-line treatment, which could improve patient prognosis and survival. Methods: In this real-world study, we retrospectively analyzed 82 patients with stages I to III breast cancer who had been analyzed by molecular residual disease (MRD) assay. A total of 82 tumor tissues and 224 peripheral blood samples were collected and detected by next-generation sequencing (NGS) based on a 1,021-gene panel in this study. Results: MRD positivity was detected in 18 of 82 patients (22.0%). The hormone receptor-/human epidermal growth factor receptor 2+ (HR-/HER2+) subgroup had the highest postoperative MRD detection rate at 30.8% (4/13). The BRCA2 and SLX4 genes were significantly enriched in all patients in the MRD positive group and FGFR1 amplification was significantly enriched in the MRD negative group with HR+/HER2-. The number of single nucleotide variants (SNVs) in tissue samples of MRD-positive patients was higher than that of MRD-negative patients (11.94 vs. 8.50 SNVs/sample). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that there was a similar biological function of the tumor-mutated genes in the 2 MRD status groups. Conclusions: This real-world study confirmed that patient samples of primary tumor tissue with different MRD status and molecular subtypes had differential genetic features, which may be used to predict patients at high risk for recurrence.

[Purification function and ecological services value of Crassostrea sp. in Yangtze River estuary].

Oyster reef ecosystem is a natural decontamination plant of estuarine environment. This paper analyzed the bioaccumulation of heavy metals by Crassostrea sp. population at the dams of Yangtze River estuary, with its purification capacity and ecological services value assessed. The results indicated that Crassostrea sp. had a high capacity in bio-accumulating Cu, Zn and Cd, with the bio-concentration factor (BCF) and biota-sediment accumulation factor (BSAF) being (14.28 +/- 2.41) x 10(3), (12.75 +/- 2.02) x 10(3) and (14.51 +/- 3.71) x 10(3), and 26.78 +/- 4.53, 23.24 +/- 3.69 and 16.62 +/- 4.25, respectively. The bioaccumulation capacity decreased in the order of Cu > Zn > Cd > As > Pb > Hg. The total weight and fresh meat weight of the oyster at the dams of Yangtze River estuary were about 1.07 x 10(6) t and 1.75 x 10(5) t, respectively, and the total storage of nutrients and heavy metals were 1.462 x 10(6) kg N, 1 x 10(5) kg P, 24 745 kg Cu, 58 257 kg Zn, 609 kg Pb, 254 kg Cd, 0.18 kg Hg and 329 kg As. The total ecological services value of the oyster reef was estimated at about 8.27 x 10(6) RMB x a(-1), including habitat value of about 5.10 x 10(6) RMB x a(-1) and environmental value of about 3.17 x 10(6) RMB x a(-1). Such an environmental value was equivalent to the value of treating about 7.31 x 10(6) t combined sewage each year, and corresponded to a large municipal sewage plant with a treatment capacity about 20 000 t d(-1).