International Journal of Medical Sciences最新文献

Autophagy is a highly conserved cellular process crucial for maintaining cellular homeostasis by degrading damaged organelles and misfolded proteins. Emerging evidence highlights its pivotal role in endometrial diseases, including endometriosis, endometritis, and endometrial cancer, where dysregulated autophagy contributes to pathogenesis through mechanisms such as altered hormone signaling, inflammation, and metabolic reprogramming. In this review, we comprehensively summarize the molecular machinery of autophagy, its regulatory networks, and its dual roles in endometrial physiology and pathology. Furthermore, we discuss the molecular mechanisms underlying autophagy in endometrial diseases, and the therapeutic potential of targeting autophagy pathways. By integrating recent advances, this review provides insights into autophagy's complex interplay with endometrial diseases and its implications for future research and therapeutic applications.

Background: Neurofibromatosis type 2 (NF2), currently more accurately named NF2-related schwannomatosis (NF2-SWN), is classified as a multiple tumor syndrome, caused by impaired expression of the merlin protein. Approximately 50% of affected individuals inherit a germline mutation from their parents, while reports on the somatic mutation landscape of other genes are infrequent. Aim: To further explore the somatic mutations of NF2-SWN and provide a theoretical basis for the treatment of NF2-SWN. Design: A retrospective study was conducted to follow up on NF2-SWN patients who underwent surgical treatment in the Department of Neurosurgery of Xiangya Hospital. Whole-exome sequencing (WES) was performed on patients with a clear family history. Methods: This study compiled clinical data from 29 patients diagnosed with NF2-SWN, conducted WES on 7 patients with well-documented genetic histories, and subsequently analyzed their genetic mutations. Results: Whole-exome sequencing identified frequent somatic mutations in genes such as TTN, FLG, CR2, and FSIP2. Missense mutations and C>T transitions were the most common alteration types. Conclusion: TTN, CR2, FLG, and FSIP2 demonstrated elevated mutation frequencies in these familial NF2-SWN patients, indicating that these mutations may contribute to the development and progression of familial NF2-SWN.

This research evaluated the antioxidant activities (in vitro and in vivo) and serum lipid profile of the chloroform (CETC) and ethanol (EETC) extracts of Theobroma cacao seeds in nitro-L-arginine methyl esters (L-NAME)-induced hypertension in Wister rats. Parameters investigated include DPPH, nitric oxide scavenging ability, CAT, GPX, SOD and serum MDA concentration. Serum lipid profiles such as total cholesterol, HDL, LDL, VLDL and TG were also assayed. The rats were treated with 100mg/kg, 200mg/kg and 300mg/kg b. w of ethanol and chloroform extracts of T. cacao and a standard drug concurrently with L-NAME. The results showed a dose-dependent increase in the antioxidant activities of EETC and CETC across all the invitro parameters with the ethanol extracts consistently outperforming the chloroform extracts. Total cholesterol, low-density lipoproteins, very low-density lipoprotein, TGs, and serum MDA showed significant (p<0.05) decreases in comparison with the control. On the other hand, there were significant (p<0.05) increases in high-density lipoproteins, GPx, SOD, CAT, and serum Nitric Oxide in the treated rats relative to the untreated rats. The observed antihypertensive properties of the extracts support that T. cacao may be useful in the management of cardiovascular health. The active constituents of these extracts could protect against hypertension.

Thyroid cancer (TC) is the most common endocrine malignancy, with anaplastic thyroid cancer (ATC) being the most aggressive subtype. Evodiamine (EVO), a bioactive compound derived from Evodia rutaecarpa, possesses anti-inflammatory and anti-tumor properties, though its effects on ATC remain underexplored. This study investigated the anticancer potential of EVO using ARO and SW579 ATC cell lines in both in vitro and in vivo models. EVO significantly inhibited cell proliferation, induced G2/M phase arrest, and increased the sub-G1 population, indicating growth inhibition and cell death. Mechanistically, EVO activated the intrinsic caspase-dependent apoptotic pathway and triggered autophagy, as shown by autophagosome accumulation and elevated LC3-II levels. Importantly, blocking autophagy attenuated caspase activation, suggesting that autophagy contributes to EVO-induced apoptosis. Moreover, oral EVO administration markedly suppressed tumor growth in a nude mouse xenograft model without causing liver or kidney toxicity. TUNEL assay further confirmed enhanced tumor cell apoptosis in vivo. These results highlight EVO as a promising therapeutic candidate for ATC by simultaneously activating autophagy and apoptosis pathways.

Several types of vaccines have been developed to manage the coronavirus disease 2019 (COVID-19) pandemic. Although COVID-19 vaccines have demonstrated reasonable efficacy, cases of cardiac, vascular and renal complications have been observed. Herein, the association between COVID-19 vaccination and subsequent renal dysfunction and mortality was analyzed using data collected from TriNetX. A retrospective cohort study was conducted of patients vaccinated against COVID-19. After exclusion and matching, a total of 1,454,791 patients each were included in the vaccinated and unvaccinated groups. The primary outcome measured was renal dysfunction and mortality. In total, 15,809 and 11,801 of AKI, and 1,513 and 697 of dialysis treatment were observed in the vaccinated and unvaccinated groups, respectively. After one year, the vaccinated group exhibited significantly higher incidences of AKI (HR: 1.20, 95% CI:1.18-1.23), and dialysis (HR: 1.84, 95% CI:1.68-2.01) than the unvaccinated group. The vaccinated group exhibited significant lower incidences of mortality (HR: 0.88, 95% CI:0.85-0.91) than the unvaccinated group. The cumulative probability of AKI and dialysis was significantly higher in the vaccinated group than the unvaccinated group. In conclusion, COVID-19 vaccination was associated with a higher risk of developing acute kidney injury, but lower rate of mortality.

Endoplasmic reticulum (ER) stress plays a pivotal role in tumor progression. As research in tumor biology advances, the relationship between ER stress and tumor initiation, development, and immune regulation has increasingly attracted attention. ER stress activates the unfolded protein response (UPR), thereby affecting key processes in tumor cells, including metabolism, proliferation, invasion, metastasis, and drug resistance. Moreover, it modulates tumor immune responses by regulating the functions of immune cells within the tumor microenvironment. This review consolidates the concept of ER stress as a central signaling hub that dictates cell fate and extensively remodels the tumor ecosystem. From a clinical perspective, this understanding provides a strong rationale for therapeutically targeting the UPR, suggesting that combining ER stress modulators with immunotherapy represents a promising strategy to overcome therapeutic resistance and improve patient outcomes.

Background: Dysregulation of N6-methyladenosine (m6A) RNA modification plays a critical role in the development and progression of non-small cell lung cancer (NSCLC). Methods: To explore the m6A modification landscape in NSCLC, we utilized direct RNA nanopore sequencing (dRNA-seq) to compare m6A patterns between NSCLC and adjacent normal tissues. Results: Our analysis revealed distinct m6A modification differences, with tumor tissues showing reduced m6A density compared to normal tissues. Aberrantly modified genes, such as SOX2 and TOP2A, exhibited hypomethylated m6A modifications and were upregulated in NSCLC tissues. We identified 14,419 differentially methylated m6A sites, with 49.5% hypermethylated and 50.5% hypomethylated. Functional enrichment analysis showed that hypermethylated genes were involved in DNA replication and transcription regulation, while hypomethylated genes were linked to cell migration and MAPK signaling. The expression patterns of m6A regulators, including METTL3, METTL16, CBLL1, FTO, ALKBH5, and ELAVL1, were consistent across NSCLC subtypes. Furthermore, correlation with clinical data from the TCGA database revealed that m6A-associated DEGs, such as HMGA1, ERO1A, LRFN4, SNTN, SLC2A1, DNASE2B, and VSIG2, were prognostically significant in NSCLC. Conclusions: This study underscores the pivotal role of m6A modifications in NSCLC and highlights the potential of dRNA-seq for identifying RNA epigenetic changes that may serve as novel therapeutic targets.

Background: Second primary malignancy (SPM) significantly impacts the survival of patients. This study endeavors to identify risk and prognostic factors of developing SPM after the first primary kidney cancer (FPKC), develop nomograms and explore potential mechanisms to optimize treatment strategies. Methods: Data of patients diagnosed with FPKC between 2000 and 2020 were obtained from the SEER database. The standardized incidence ratio (SIR) was calculated to assess the relative risk of developing SPM in FPKC patients. Competing risk model as well as Cox regression analyses were employed to identify independent risk and prognostic factors, and nomograms were constructed and evaluated. Finally, to understand how FPKC influences the risk of developing SPM, we carried out Mendelian randomization (MR) and transcriptome-wide association study (TWAS) analyses. Results: A total of 72408 and 5295 patients were included in stage I and II analysis, respectively. Risk distribution analysis revealed that FPKC patients exhibited a higher SPM risk than general population (SIR = 1.42, 95% CI: 1.40-1.44). Independent predictive factors were identified for model construction, and nomograms were developed. AUC of ROC, calibration curves and DCA illustrated excellent calibration and clinical applicability of the models. MR analyses indicated that kidney cancer might causally increase the risk of cancer in stomach, colon, rectum, lung, prostate, bladder, skin and eye. TWAS analysis identified 19 susceptibility genes associated with four types of cancers. Conclusion: This study successfully established nomograms, delving into the potential mechanisms of developing SPM after FPKC. All these findings will promote the optimization of treatment strategies.

Radiation pneumonitis (RP) is a common complication of radiotherapy that significantly limits the tolerable radiation dose, thereby compromising treatment outcomes. In severe cases, it can become life-threatening. Currently, the management of RP relies primarily on glucocorticoids. However, this approach is associated with several drawbacks, including markedly increased risks of immunosuppression and infection, metabolic disturbances, musculoskeletal injury, gastrointestinal adverse effects, and most importantly- a potential compromise of antitumor efficacy. Moreover, current treatments for RP and radiation induced pulmonary fibrosis remain unsatisfactory, underscoring the need for mechanistic studies and the exploration of novel therapeutic targets and strategies. RP and lipopolysaccharide (LPS) -induced pneumonitis, originating from Gram-negative bacteria, represent two distinct forms of pulmonary inflammation. We compare their molecular mechanisms-with both shared pathways and key distinctions despite clinical similarities-and explore diverse therapies, including anti-inflammatory responses, antioxidant defenses, gut microbiota regulation, cell death modulation, mitophagy enhancement, among others. In particular, we highlight therapies and targets that have shown efficacy in LPS-induced pneumonitis but have not yet been investigated in the context of RP. These insights may offer valuable guidance for both clinical management and fundamental research on RP.

With the increasing prominence of cancer immunotherapy, therapeutic tumor vaccines have emerged as a promising strategy to enhance antitumor immunity by increasing tumor immunogenicity and activating the patient's immune system to inhibit tumor growth. However, their clinical efficacy is often limited due to insufficient immune cell infiltration, low antigen immunogenicity, and tumor immune escape mechanisms. To address these challenges, various innovative approaches have been explored, including the optimization of tumor antigen selection, the development of advanced vaccine platforms, and the combination of vaccines with other treatment strategies such as radiotherapy, chemotherapy, immune checkpoint inhibitors (ICIs), cytokine therapy, and adoptive T-cell transfer. This review provides a comprehensive summary of the mechanisms underlying tumor antigen vaccines, discusses recent advancements in vaccine design and combinatorial strategies, and assesses their potential to enhance therapeutic outcomes. We also highlight the ongoing challenges and future directions, underscoring the importance of interdisciplinary efforts to realize the full potential of tumor vaccines as a foundation of personalized cancer immunotherapy.