Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Redox-active endosomes mediate α5β1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.

Mechanical cues sensed by integrins induce cells to produce proteases to remodel the extracellular matrix. Excessive protease production occurs in many degenerative diseases, including osteoarthritis, in which articular cartilage degradation is associated with the genesis of matrix protein fragments that can activate integrins. We investigated the mechanisms by which integrin signals may promote protease production in response to matrix changes in osteoarthritis.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Trans-Lesion Synthesis and Mismatch Repair Pathway Crosstalk Defines Chemoresistance and Hypermutation Mechanisms in Glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival.

Inhibition of UBA6 by inosine augments tumour immunogenicity and responses.

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity.

Five EMT-related genes signature predicts overall survival and immune environment in microsatellite instability-high gastric cancer.

Background: Microsatellite instability-high (MSI-H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI-H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood.

The kinase activity of integrin-linked kinase regulates cellular senescence in gastric cancer.

The activity of integrin-linked kinase (ILK) in cancerous cells is often oncogenic and associated with malignant properties, such as uncontrolled cell cycle progression and evasion from senescence. However, the role of ILK in cellular senescence in gastric cancer (GC) has not been previously examined. We generated single-cell clones of ILK knock-out using CRISPR-Cas9 in human GC lines with mesenchymal or epithelial histology.

Identification of potentially functional circRNAs and prediction of circRNA-miRNA-mRNA regulatory network in periodontitis: Bridging the gap between bioinformatics and clinical needs.

Background And Objective: Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue-dependent and disease-dependent. This study aimed to identify novel periodontitis-associated circRNAs and predict relevant circRNA-periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic.

Complete loss of miR-200 family induces EMT associated cellular senescence in gastric cancer.

The EMT (epithelial-to-mesenchymal-transition) subtype of gastric cancer (GC) is associated with poor treatment responses and unfavorable clinical outcomes. Despite the broad physiological roles of the micro-RNA (miR)-200 family, they largely serve to maintain the overall epithelial phenotype. However, during late-stage gastric tumorigenesis, members of the miR-200 family are markedly suppressed, resulting in the transition to the mesenchymal state and the acquisition of invasive properties.

Unravelling roles of error-prone DNA polymerases in shaping cancer genomes.

Mutagenesis is a key hallmark and enabling characteristic of cancer cells, yet the diverse underlying mutagenic mechanisms that shape cancer genomes are not understood. This review will consider the emerging challenge of determining how DNA damage response pathways-both tolerance and repair-act upon specific forms of DNA damage to generate mutations characteristic of tumors. DNA polymerases are typically the ultimate mutagenic effectors of DNA repair pathways.

Rad18 mediates specific mutational signatures and shapes the genomic landscape of carcinogen-induced tumors .

The E3 ubiquitin ligase Rad18 promotes a damage-tolerant and error-prone mode of DNA replication termed trans-lesion synthesis that is pathologically activated in cancer. However, the impact of vertebrate on cancer genomes is not known. To determine how Rad18 affects mutagenesis , we have developed and implemented a novel computational pipeline to analyze genomes of carcinogen (7, 12-Dimethylbenz[a]anthracene, DMBA)-induced skin tumors from and mice.

Injectable photo crosslinked enhanced double-network hydrogels from modified sodium alginate and gelatin.

Recently, photocrosslinked hydrogels have attracted more and more attention in biomedical applications. In this study, a serials of injectable hydrogels were fabricated from aldehyde methacrylate sodium alginate and amino gelatin (AMSA/AG) using a two-step process. Here, sodium alginate, a kind of natural polysaccharide, was modified by oxidizer to form aldehyde sodium alginate (ASA), and methacrylate groups were further grafted on the main chain of ASA.

[NEW PROGRESS OF ACELLULAR FISH SKIN AS NOVEL TISSUE ENGINEERED SCAFFOLD].

Objective: To review the recent research progress of acellular fish skin as a tissue engineered scaffold, and to analyze the feasibility and risk management in clinical application.

Methods: The research and development, application status of acellular fish skin as a tissue engineered scaffold were comprehensively analyzed, and then several key points were put forward.

Results: Acellular fish skin has a huge potential in clinical practice as novel acellular extracellular matrix, but there have been no related research reports up to now in China.

Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive.

Soft tissue adhesives made from natural hydrogel are attractive in clinical applications due to their excellent properties, such as high water content, good biocompatibility, low immune, good biodegradability. Hydrogels derived from natural polysaccharides and proteins are ideal components for soft tissue adhesive since they resemble the extracellular matrices of the tissue composed of various sugar and amino acids-based macromolecules. In this paper, a series of novel tissue adhesives mixed by aldehyde sodium alginate (ASA) with amino gelatin (AG) were developed and characterized.

[PROGRESS OF ALGINATE DERIVATIVES BASED ON BIOMEDICAL MATERIALS].

Objective: To summarize the current research status of alginate derivatives based on biomedical materials, and analyze several key points as novel clinical products.

Methods: The general preparation and application methods of alginate derivatives based on biomedical materials at home and abroad were reviewed. The present status and problems were analyzed.

Calcium alginate enhances wound healing by up-regulating the ratio of collagen types I/III in diabetic rats.

Calcium alginate has been proved to favor the skin ulcer healing and collagen synthesis was a critical factor for the wound closure. The present study was to elucidate the mechanism of calcium alginate on the diabetes skin ulceration. Calcium alginate dressing was applied daily on the full-thickness exercising wound created on the back of diabetic rat model as Alg-group (n=6), and the vaseline dressing was used as control (n=6).

[Application status and research progess of alginate dressings].

Objective: To review the application status and research progress of alginate dressings.

Methods: The related home and abroad literature was reviewed, and the relevant product standards and regulations were summarized.

Results: Alginate dressings have been widely used in clinical because of the characteristics of anti-infection and promoting wound healing.

[Progress of alginate-based biomedical materials].

Objective: To review the current situation of alginate-based biomedical materials, especially focus on the clinical strategies and research progress in the clinical applications and point out several key issues that should be concerned about.

Methods: Based on extensive investigation of domestic and foreign alginate-based biomedical materials research and related patent, literature, and medicine producted, the paper presented the comprehensive analysis of its research and development, application status, and then put forward several new research directions which should be focused on.

Results: Alginate-based biomedical materials have been widely used in clinical field with a number of patients, but mainly in the fields of wound dressings and dental impression.

[Product standard and quality control of sodium hyaluronate].

Objective: To analyze and compare the domestic quality standard and foreign quality standard of sodium hyaluronate (HA), and to expatiate on the critical process monitoring parameters.

Methods: Different quality standards of HA were compared by translating and sorting, and some experimental data were analyzed as well as the manufacturing practice was elaborated.

Results: Differences exist in raw materials standard or specifications of products between domestic and foreign, but the basic control points are concordant.

[Research progress of viscosupplementation].

Objective: To carry out a comprehensive and objective evaluation of viscosupplementation, so as to provide the actual judgments of effectiveness, development trends, and direction.

Methods: The related literature was reviewed, and the keys were the assessments from the international relevant advisory bodies and insurance companies and the evidence-based medicine on clinic.

Results: Viscosupplementation has been gradually accepted.

[Properties, products, and applications of chitosan].

Objective: To review and analyze the properties, products, and applications of chitosan so as to explore the key molecular structure parameters which can affect the properties and applications significantly, and to reveal the relationship between molecular structures and properties so as to provide reference for further development of chitosan industry and scientific research.

Methods: Based on the collection and analysis of related literature, patents and medical products derived from chitosan, as well as the author's experiences in research and development, evaluation and standardization of chitosan, the paper was prepared to bring more attentions into the correlativity between structure and properties of chitosan.

Results: Potential risks in clinical application of chitosan-based preparations were seriously proposed in addition to a scientific review and analysis on relationships between chitosan structure and properties, as well as the present situations of developments and applications of chitosan.

A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions' prevention.

Post-operative peritoneal adhesions are common and serious complications for surgeons. They can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We synthesized injectable hydrogels that formed by chemical modification through grafted hydrobutyl groups to chitosan chains.

[Technics of inactivating/removing medical chitosan pathogen].

Objective: To verify the technics of inactivating/removing pathogens in medical chitosan derived from shrimp shell.

Methods: Possible pathogen species were included according to the raw material of shrimp shell used in production, then bacillus cereus, porcine parvovirus (PPV) and pseudorabies virus (PRV) were selected as indicator pathogens. Pathogen solution was prepared in accordance with Technical Standard for Disinfection.

[Study on treating residual cavity of body surface after abscess drainage by sodium hyaluronate hydrogel].

Objective: To study the effect of sodium hyaluronate hydrogel in treating residual cavity on body surface after abscess drainage so as to provide new method to speed up the healing of residual cavity after body surface abscess drainage and reduce the frequency of dressing change and clinic nursing workload.

Methods: From June 2007 to March 2008, 60 outpatients with body surface abscess drainage were randomly divided into hydrogel group (group A, 30 cases) and the control group (group B, 30 cases). In group A, there were 16 males and 14 females aged (49.