Research Medical Center

BACKGROUND:Colorectal cancer (CRC) encompasses various cancers located in the rectosigmoid junction, rectum, and anus, as well as parts of the colon. Globally, CRC is the second leading cause of cancer-related mortality and the third most prevalent malignancy. The KRAS oncogene was found to be mutated in 30 to 50% of CRC cases, leading to dysregulated cellular functions. Furthermore, the connection between KRAS and P53 gene mutations and the incidence of both colorectal and breast cancer remains an area of interest. METHODS:This comprehensive narrative review was carried out by mining data from recognized databases, such as PubMed, Google Scholar, and ResearchGate. The purpose was to extensively explore and understand the association between the KRAS and P53 gene mutations and the prevalence of colorectal and breast cancers. RESULTS:The mutation in the KRAS oncogene has been identified as a key player in cellular signaling pathways, including MAPK, PI3K, and PLD. Despite extensive research, gene therapies targeting these mutations have seen limited success, especially in codons 12, 13, 61, and 143. CONCLUSION:Mutations in the KRAS and P53 genes, along with aberrant MDM2 expression, play pivotal roles in the onset and progression of colorectal cancer by disrupting key cellular signaling pathways, such as MAPK, PI3K, and PLD. Despite advancements in understanding these mechanisms, current gene therapy approaches have shown limited success, particularly in targeting KRAS codon mutations. This underscores the urgent need for innovative therapeutic strategies and further research to develop effective treatments for colorectal cancer and its potential links to other malignancies, such as breast cancer.

The clinical management of bone defects presents a significant challenge in regenerative medicine due to the limited self-repair capacity of bone tissue and inadequate vascularization. Nitric oxide, a gaseous signaling molecule, has garnered attention as a potent modulator of bone remodeling, exhibiting pro-osteogenic, pro-angiogenic, and anti-inflammatory properties. However, its therapeutic application is limited by its short half-life, high reactivity, and dose-dependent biphasic effects. Advanced polymer-based nanoformulations have been developed to address these challenges and enable controlled and localized NO delivery to bone tissue. This review explores role of NO in bone repair mechanisms and the limitations of conventional delivery systems. Significant focus is given to innovative polymeric platforms, such as dendrimers, micelles, nanogels, and hybrid composites, which offer precise control over release kinetics, high encapsulation efficiency, and targeted delivery. Additionally, integrating NO delivery within nanoengineered scaffolds and coatings for orthopedic implants is explored as a promising strategy to enhance osteointegration and reduce the risk of post-surgical infections. Preclinical studies demonstrate promising osteogenic effects yet face significant challenges including cytotoxicity at elevated NO concentrations along with non-standardized evaluation protocols and scalability limitations. Future perspectives point to the potential of stimuli-responsive systems, co-delivery approaches, and personalized strategies utilizing additive manufacturing technologies. This review consolidates the latest advancements in the field, underscoring the significant potential of polymer-based NO nanoformulations to revolutionize bone tissue engineering.

Liver fibrosis, a chronic progression process of liver disease in which various factors damage the liver, leading to the development of liver inflammation and eventually progressing to liver cirrhosis. Food-medicine plants, which serve dual roles in nutrition and therapy, play a significant role in the management of chronic diseases, particularly within minority communities and developing regions. This review systematically examines the therapeutic potential of bioactive compounds derived from food-medicine plants-such as flavonoids, alkaloids, phenolics, and terpenoids-in mitigating liver fibrosis. These compounds exert their effects through multiple mechanisms, including modulation of key signaling pathways such as TGF-β, PI3K/Akt, ferroptosis, and Wnt/β-catenin. Additionally, they enhance antioxidant enzyme activity, suppress pro-fibrotic mediators, and reduce fibrosis-related biomarkers. Overall, this work underscores the multifaceted mechanisms underlying the anti-fibrotic effects of food-medicine plant products. Nevertheless, further clinical validation is necessary to translate these preclinical insights into effective therapies, thereby providing a foundation for future research and drug development in the management of liver fibrosis.

Introduction:Obesity is a well-established risk factor for asthma pathogenesis. However, the underlying mechanisms remain incompletely understood, and effective therapeutic interventions are currently lacking, making asthma management in obese individuals particularly challenging. Asthma is characterized by chronic airway inflammation, eosinophilic infiltration, and airway hyperresponsiveness (AHR). In this study, we investigated the novel role of fibroblast growth factor 21 (FGF21), a stress-inducible hepatokine with pleiotropic metabolic regulatory functions, in obesity-associated AHR using a diet-induced obesity mouse model (n = 10). Material and Methods:Serum samples were collected from obese and lean asthma patients, along with relevant clinical indicators, including body mass index (BMI), forced expiratory volume in 1 second (FEV1%), and the FEV1/forced vital capacity (FVC) ratio, to facilitate the investigation. Moreover, diet-induced obese mice with innate AHR (male, n = 10) were employed to clarify the effects of FGF21 and FGF21-neutralizing antibody on obesity induced AHR. In vitro, LAD2 human mast cells and P815 murine mast cells activated by compound 48/80 were used to elucidate the underlying mechanisms. Results:Our findings demonstrate that serum FGF21 levels exhibit reportedly elevated in participants with obesity and are associated with impaired pulmonary function. In diet-induced obese (DIO) mice, FGF21 levels were increased in both serum and bronchoalveolar lavage fluid (BALF). In vivo investigations demonstrate that administration of recombinant FGF21 exacerbated AHR in DIO mice, whereas FGF21-neutralizing antibody treatment ameliorated obesity-induced AHR and suppressed mast cell infiltration. Mechanistically, FGF21 was found to potentiate mast cell activation through cholesterol biosynthesis modulation. Crucially, pharmacological inhibition of FGFR1 abrogated FGF21-induced mast cell hyperactivity and cholesterol synthesis, indicating FGFR1-dependent signaling in this process. Conclusion:These findings may represent the FGF21/FGFR1 axis as a potential therapeutic target for obesity-related AHR and asthma.

Background:Staphylococcus argenteus, a member of the Staphylococcus aureus complex, has increasingly been recognized as a human pathogen but is frequently misidentified as S. aureus in routine clinical laboratories. Reports of prosthetic joint infection (PJI) caused by this species remain rare. Methods:We describe a case of delayed-onset PJI in a 71-year-old woman following total knee arthroplasty. Repeated conventional cultures were negative after empirical vancomycin therapy. Metagenomic next-generation sequencing (mNGS) of wound exudate detected S. argenteus, which guided extended culture and subsequent isolation of low-abundance colonies. Species identification was confirmed by whole-genome sequencing (WGS), multilocus sequence typing (MLST), and reinterpretation of MALDI-TOF MS results. Antimicrobial susceptibility testing (AST) was performed and compared with WGS-based resistance prediction. Phylogenetic analysis was conducted using 452 publicly available S. argenteus genomes. Aim:This study aimed to describe the clinical diagnosis, microbiological identification, and genomic characterization of a Staphylococcus argenteus strain causing prosthetic joint infection. Results:The isolate was identified as sequence type ST2250 and lacked the staphyloxanthin operon, consistent with the non-pigmented phenotype. WGS and phenotypic AST showed 100% concordance across 11 clinically relevant antibiotics. Phylogenomic analysis revealed that the strain clustered closely with Southeast Asian lineages. Following targeted therapy with intravenous vancomycin and surgical wound management, the patient showed rapid clinical improvement with resolution of local inflammation and complete wound healing. Conclusion:This is the first confirmed case of S. argenteus PJI in Suzhou, China. The case highlights the diagnostic value of mNGS in culture-negative PJI, the importance of molecular tools for correctly differentiating S. argenteus from S. aureus, and the potential of WGS to support resistance prediction for rare staphylococcal pathogens.