International Journal of Medical Sciences最新文献

Background: Previous observational studies have observed associations between rheumatoid arthritis (RA), knee osteoarthritis (KOA), hip osteoarthritis (HOA), and frailty, but the causal relationships remain unestablished. Objective: This study aimed to evaluate the causal relationships between RA, KOA, HOA, KneeHipOA, and frailty using Mendelian randomization (MR) and bioinformatics analysis. Methods: We performed two-sample MR to test for causality between RA, KOA, HOA, KneeHipOA, and frailty. Subsequently, we combined our results in a meta-analysis and conducted multiple sensitivity analyses (MR-Egger, weighted median, constrained maximum likelihood and model averaging (cML-MA), and Bayesian weighted MR (BWMR)). We further explored the role of circulating immune cells and the effects of RA and OA-related gene expression on frailty. Results: Genetically determined RA, KOA, HOA, and KneeHipOA were correlated with a higher risk of frailty. The results of multivariate MR analyses were consistent with those of two-sample MR. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis indicated that RA and OA-related genes were primarily enriched in various immune responses. Our findings suggested that increases in monocyte cell AC, eosinophil cell AC, and neutrophil cell AC were associated with a higher risk of frailty. Conclusion: This research provides evidence supporting the associations between RA, KOA, HOA, KneeHipOA, and frailty. It also highlights the significant role of circulating immune cells in the development of frailty, indicating the importance of frailty management from an immunological perspective.

Background: Carotene exists naturally in a complex mixture consisting of alpha (α), beta (β), and gamma (γ)-isoforms. Previous studies investigated the effects of individual carotene isomers on bone rather than their actions in a mixture. Purpose: This study explored the bone-protective properties of palm carotene mixture using both two- and three-dimensional co-culture systems. Study design: The viability of human foetal osteoblasts (hFOB 1.19), viability of human monocytic cell line (THP-1), osteoblast differentiation, osteoclast maturation, bone quality and strength were assessed in two- and three-dimensional co-culture system after treatment of palm carotene mixture. Methods: The viability of hFOB 1.19 and THP-1 was determined on day 1, 3, and 6 following treatment of palm carotene mixture. The osteoblast-osteoclast co-culture (ratio of hFOB 1.19 to THP-1 = 2:1) was treated with palm carotene mixture as well as subjected to alkaline phosphatase (ALP) and tartrate resistant acid phosphatase (TRAP) staining on day 21 to assess the osteoblast proliferation and osteoclast maturation. Dual-energy X-ray absorptiometry, micro-computed tomography, universal testing machine, and bone histomorphometry were used to assess the bone parameters of scaffolds co-cultured with osteoblasts and osteoclasts. Results: Palm carotene mixture (3.13 - 50 μg/mL) increased osteoblast viability. Monocyte viability decreased in lower concentration (3.13 - 12.5 μg/mL) but increased in higher concentration (25 - 50 μg/mL) of palm carotene mixture. Treatment with palm carotene mixture (12.5 µg/mL) demonstrated earlier peak for the ALP-positive area on day 14 but decreased total number of TRAP-positive multinucleated cells on day 21. Palm carotene mixture also increased bone volume and osteoblast number in the three-dimensional co-culture system. Conclusion: Palm carotene mixture potentially exhibits beneficial effects on bone by accelerating osteoblast proliferation and suppressing osteoclast maturation. The findings of current study serve as the basis for the further validation through animal experiments and human trials.

Nucleus accumbens-associated protein 1 (NACC1) regulates various types of biological processes. It is a transcription factor associated with cancer. NACC1 is overexpressed in many human malignancies and can regulate the progression, metastasis, and drug resistance of cancer cells. However, its precise role in acute myeloid leukemia (AML) remains unknown. This study aimed to unravel the basic mechanism of NACC1 in AML. Our findings demonstrated that NACC1 is immensely expressed in AML cells. Lentiviral vector-mediated knockdown of NACC1 inhibited the PI3K/AKT signaling pathway. Simultaneously, NACC1 knockdown promoted apoptosis, suppressed the proliferative capacity of AML cells, and resulted in cell cycle arrest during the G0/G1 phase. Additionally, A disintegrin and metalloproteinase 9 (ADAM9) was markedly expressed in AML cells. NACC1 regulated ADAM9 expression. ADAM9 expression was also downregulated after NACC1 knockdown. Concurrently, ADAM9 knockdown affected the activity of AML cells by decelerating the growth rate, promoting apoptosis, and blocking cell cycle progression. In addition, the AKT activator SC79 restored the inhibited cell proliferation after NACC1 knockdown and ADAM9 knockdown. In conclusion, our study suggested that the NACC1/ADAM9/PI3K/AKT axis is crucial for sustaining the survival of AML cells, indicating that NACC1 may be a viable target for treating AML.

Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality rates globally. Advances in single-cell sequencing technology have enabled comprehensive analyses of tumor cells at single-cell resolution, providing valuable insights into the molecular mechanisms underlying CRC initiation and progression. In this study, we integrated single-cell sequencing data with the TCGA database to identify key molecular pathways involved in CRC pathogenesis. Our analysis revealed that dysregulation of phospholipid metabolism, particularly sphingolipid metabolism, plays a crucial role in CRC development. Specifically, we observed aberrant expression of genes involved in sphingolipid biosynthesis and degradation, as well as altered levels of various sphingolipid metabolites in CRC cells. Furthermore, we identified several potential therapeutic targets, including SMPD1, GLTP, B3GALT4, and ST8SIA6, within the sphingolipid metabolism pathway that could be exploited for the development of novel CRC treatments. Overall, our findings provide novel insights into the molecular mechanisms underlying CRC and highlight the importance of targeting phospholipid metabolism, specifically sphingolipid metabolism, as a potential therapeutic strategy for CRC.

The outbreak of COVID-19 has opened up new avenues for exploring the importance of vitamin D in immunity, in addition to its role in calcium absorption. Recently, vitamin D supplementation has been found to enhance T regulatory lymphocytes, which are reduced in individuals with COVID-19. Increased risk of pneumonia and increases in inflammatory cytokines have been reported to be major threats associated with vitamin-D deficiency. Although vaccination reduces the threat of COVID-19 to a certain extent, herd immunity is the long-term solution to overcoming such diseases. Co-administration of vitamin D with certain inactivated vaccines has been reported to enhance the systemic immune response through stimulation of the production of antigen-specific mucosal immunity. COVID-19 was found to induce multiple organ damage, and vitamin D has a beneficial role in various organs, such as the intestines, pancreas, prostate, kidneys, liver, heart, brain, and immune cells. The consequences that occur after COVID-19 infection known as long COVID-19 are also a concern as they accumulate and target multiple organs, leading to immune dysregulation. The present review covers the overall role and impact of vitamin D and its deficiency for various organs in normal conditions and after COVID-19 infection, which is still a serious issue.

Background: Recent research emphasizes the significant regulatory functions of epigenetic alterations and post-translational modifications (PTMs) in the ferroptosis process. Despite the existing volume of literature, there is a remarkable shortage of comprehensive analyses that systematically trace the evolution of research, map key investigative routes, evaluate the current situation of the field, determine central themes, and predict future directions. This study intends to offer a comprehensive summary of the progress achieved during the past 12 years in comprehending how epigenetic modifications and PTMs regulate ferroptosis. Methods: The dataset originated from the Web of Science, covering the period from January 1, 2012, to May 21, 2024. By employing advanced analytical tools, we carried out an extensive scientometric assessment in combination with detailed visual data analysis. Results: The results emphasize the crucial role of China, which contributes 69.59% of the global research output, thereby demonstrating its significant influence on the research trajectory in this domain. Remarkable productivity is manifested at institutions such as Central South University, Shanghai Jiao Tong University, and Zhejiang University. Liu Shuang and Tang Daolin stand out as the most productive authors in this field. The journal Cell Death & Disease leads in terms of publication volume, having published the greatest number of articles related to this area. This study identified hepatocellular carcinoma, mitochondrial diseases, and iron overload as the most prominent diseases explored in this research domain. Conclusion: This meticulous scientometric assessment is beneficial to both experienced researchers and newcomers by providing essential information and facilitating the derivation of innovative concepts in this field.

Background: Recent studies suggest a potential link between HS and renal dysfunction. Our objective is to assess the correlation between hidradenitis suppurativa (HS) and renal consequences, specifically focusing on acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). Methods: This study was performed based on retrospective cohort design. Electronic medical records of participants were retrieved from the US collaborative network in the TriNetX research network. Information from 46,561 individuals with HS was examined alongside an equivalent number of matched controls. Propensity matching was performed for matching confounders. The study spanned from January 1, 2005, to December 31, 2017. Primary outcomes were set as renal dysfunction, including AKI, CKD, and ESRD. Results: Over the 1-year follow-up, people with HS presented a 1.84-fold higher risk of AKI (95% CI, 1.34-2.53) and a 1.37-fold higher risk of CKD (95% CI, 1.02-1.85) than non-HS individuals. Elevated risks persisted over the longer follow-up periods for AKI at 1.51-fold (95% CI, 1.28-1.77) for 3-years-follow-up and 1.47-fold (95% CI, 1.30-1.65) for 5-years-follow-up, respectively. Stratification by sex revealed higher risks in males, and comparison with psoriasis patients indicated increased AKI and CKD risks in HS patients. Conclusion: This study highlights a significant association between HS and renal dysfunction, emphasizing the need for further exploration of shared pathophysiological mechanisms. The findings could offer potential insights into HS-related comorbidities.

Background: Chemotherapy resistance is a great challenge in the treatment of gastric cancer (GC), so it is urgent to explore the prognostic markers of chemoresistance. PUF60 (Poly (U)-binding splicing factor 60) is a nucleic acid-binding protein that has been shown to regulate transcription and link to tumorigenesis in various cancers. However, its biological role and function in chemotherapy resistance of GC is unclear. Methods: The expression and prognostic value of PUF60 in GC chemotherapy-resistant patients were analyzed by databases and K-M Plotter. The functional effect of PUF60 on chemoresistance in GC was studied by by RNA interference, CCK8 test, colony formation test and apoptosis detection. Moreover, further validation and mechanism exploration were conducted in clinical samples. Results: PUF60 was highly expressed in both GC and chemoresistant tissues, and was positively correlated with poor prognosis in GC patients treated with 5-fluorouracil (5-FU). In addition, the knockdown of PUF60 significantly reduced the proliferation of human gastric cancer cells and increased sensitivity to chemotherapy drugs, such as 5-FU and cisplatin (CDDP). Mechanistically, PUF60 enhances chemotherapy resistance in gastric cancer (GC) cells by actively excluding chemotherapy drugs via the recombinant ATP Binding Cassette Transporter A1 (ABCA1) and ATP Binding Cassette Subfamily C Member 1 (ABCC1). This process further affects the cell cycle, reduces cell apoptosis, and ultimately promotes resistance to chemotherapy in GC. Conclusion: PUF60 promotes chemoresistance in GC, resulting in poor prognosis of GC patients treated with 5-FU, and providing a new idea for overcoming the chemoresistance in GC.

Nephrotoxicity remains a significant concern associated with tyrosine kinase inhibitors, such as dasatinib (DASA). Previous studies have shown that DASA can induce renal tubular cell death, contributing to its nephrotoxic effects. In contrast, naringenin (NGN) is known for its antioxidant and anti-inflammatory properties. This study aimed to explore the nephroprotective potential of NGN against acute kidney injury induced by DASA in a mouse model. Mice were pre-treated with different doses of NGN (50, 100 mg/kg) for one week, followed by a single dose of DASA (25 mg/kg) on the 8th day. Results demonstrated that DASA significantly increased serum levels of blood urea nitrogen, creatinine, uric acid, and lactate dehydrogenase, which were effectively attenuated by NGN pretreatment. Furthermore, kidney tissues exposed to DASA exhibited elevated malondialdehyde (MDA) levels, which were significantly reduced by NGN. NGN also restored depleted levels of antioxidants (glutathione (GSH) and catalase (CAT)) in kidney tissues following DASA treatment. Additionally, NGN mitigated the upregulation of pro-inflammatory cytokines (TNF-α, NF-κB, and IL-6) induced by DASA, indicating an anti-inflammatory effect. Notably, DASA treatment upregulated the gene expression of the pro-apoptotic gene BAX while downregulating the expression of BCL-2 and Caspase-3 in kidney tissues. These findings suggest that NGN exerts nephroprotective effects against DASA-induced nephrotoxicity through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Further investigations are warranted to elucidate the underlying mechanisms involved.

Background: The prognostic significance of the red blood cell distribution width to albumin ratio (RAR) spans various diseases, yet its utility as a biomarker for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) remains unclear. Methods: We retrospectively studied 1,413 patients with HBV-HCC. Receiver operating characteristic curves identified optimal RAR cut-offs, stratifying patients into H-RAR and L-RAR groups. Propensity score matching helped balance baseline characteristics. We further evaluated the incremental predictive value of RAR by incorporating it into established conventional models. Results: Overall, 906 patients with HBV-HCC were enrolled (H-RAR group, 600 (66.2%); L-RAR group, 306 (33.8%)). After propensity score matching, 209 patients were included in each group with balanced baseline characteristics (all p > 0.05). RAR demonstrated superior prognostic discrimination compared to red blood cell distribution width, albumin, total bilirubin, and Child-Pugh scores alone, with an area under the curve (AUC) of 0.751. The risk of all-cause mortality increased progressively within a specific RAR range. High RAR was identified as an independent risk factor for long-term overall survival in patients with HBV-HCC (hazard ratio = 1.707, 95% confidence interval [CI]: 1.338-2.176). Stratification by tumour stage revealed substantially lower overall survival for H-RAR than for L-RAR across Tumour, Node, Metastasis I-IV stages. Incorporating RAR into traditional HCC staging systems substantially improved the ability to predict overall mortality risk. Conclusion: RAR is a novel and valuable prognostic indicator for patients with HBV-HCC.