Discovery Medicine[JOURNAL]
Sun
200 papers
Exploring the lncRNA NEAT1/iASPP Pathway in Chordoma: Mechanisms of Proliferation Suppression and Apoptosis Induction.
Ma Z, Wang L, Ji Z … +1 more , Li H
Discov Med · 2025 Apr · PMID 40287808 · Publisher ↗
BACKGROUND: Chordoma is a rare, primary malignant bone tumor arising from remnants of embryonic notochord tissue. While the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 () has been implicated in...
BACKGROUND: Chordoma is a rare, primary malignant bone tumor arising from remnants of embryonic notochord tissue. While the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 () has been implicated in various cancers, its role in chordoma remains to be elucidated. This study aims to elucidate the mechanisms by which lncRNA influences chordoma growth and apoptosis. METHOD: lncRNA expression was assessed in chordoma using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Two chordoma cell lines with high lncRNA expression were selected for lncRNA knockdown and inhibitor of apoptosis-stimulating protein of p53 (iASPP) overexpression experiments. Cell survival was assessed using Cell Counting Kit-8 (CCK-8) and colony formation assays, while apoptosis and iASPP expression levels were analyzed by flow cytometry, Western blotting (WB), and RT-qPCR. , treated U-CH1 cell lines were subcutaneously injected into nude mice to establish a chordoma model. Tumor apoptosis was evaluated through hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and WB was used to measure the levels of apoptosis-related proteins and iASPP in the tissues. RESULTS: The lncRNA was highly expressed in chordoma. Silencing lncRNA inhibited the survival and proliferation of chordoma cell lines MUG-Chor1 and U-CH1, and promoted apoptosis ( < 0.05). Overexpression of iASPP counteracted these effects, enhanced cell growth and inhibited apoptosis in the si-lncRNA NEAT1 group ( < 0.05). HE and TUNEL staining results indicated that silencing lncRNA reduced cell proliferation and division in chordoma tissues, and led to a marked increase in apoptosis ( < 0.05). These effects were reversed by overexpression of iASPP ( < 0.05). CONCLUSION: In chordoma, lncRNA is highly expressed, and silencing lncRNA inhibits the proliferation and induces apoptosis of chordoma cells while decreasing the expression of iASPP. These findings offer new insights into the involvement of the lncRNA /iASPP pathway in chordoma development.
Protective Role of Cerium Oxide Nanoparticle Pretreatment in Preventing Pilocarpine-Induced Epileptic Seizures.
Yang D, Yang S, Deng J … +4 more , Fan X, Jiang G, Yang F, Wang X
Discov Med · 2025 Apr · PMID 40287807 · Publisher ↗
BACKGROUND: Epilepsy is a prevalent neurological disorder characterized by transient brain dysfunction due to abnormal neuronal discharges. Oxidative stress is strongly correlated with epilepsy onset and progression and...
BACKGROUND: Epilepsy is a prevalent neurological disorder characterized by transient brain dysfunction due to abnormal neuronal discharges. Oxidative stress is strongly correlated with epilepsy onset and progression and is a critical factor in triggering seizures. Therefore, antioxidants may serve as effective anti-seizure treatments. Cerium oxide nanoparticles (CNP), which have antioxidant properties and function as nano-enzymes, may offer neuroprotective and therapeutic benefits for epilepsy. This study aims to investigate the effects of CNP on epilepsy. METHODS: We established a pilocarpine (PILO)-induced epilepsy rat model to assess the effects of pretreatment with different doses of CNP on epileptic behavioral changes, electroencephalographic activity, and nuclear factor erythroid 2-related factor 2 (NRF2) signaling in rats. RESULTS: In brief, a dose of 2.5 mg/kg CNP prolonged the latency of PILO-induced seizures in rats ( < 0.05), reduced the severity of seizures ( < 0.05), and decreased the 24-h mortality rate ( < 0.01). Additionally, CNP also extended the latency of epileptiform discharges ( < 0.01) and significantly decreased the average energy density of electroencephalographic activity ( < 0.0001). It inhibited seizure-induced lipid peroxidation ( < 0.001) and increased superoxide dismutase ( < 0.05) and catalase activities ( < 0.01). Furthermore, pretreatment with CNP elevated the expression of NRF2 and NADPH:quinone oxidoreductase 1 (NQO1) in antioxidative stress pathways ( < 0.05) and reduced neuronal necrosis and degeneration in CA1 and CA3 regions ( < 0.05). CONCLUSIONS: CNP exhibits anti-epileptic and neuroprotective effects in PILO-induced epilepsy. This protective effect is likely due to the enhancement of the NRF2 signaling pathway, which regulates antioxidant enzymes, improves neuronal defense mechanisms against oxidative stress, and reduces seizure-induced neuronal damage.
Effects of Botulinum Toxin A on Condylar Subchondral Bone Mass.
Tian L, He Y, Zhang W … +6 more , Yang W, Jiang C, He D, Mao E, Luo Y, Sheng X
Discov Med · 2025 Apr · PMID 40287806 · Publisher ↗
BACKGROUND: The management of temporomandibular disorders (TMD) remains challenging, with its underlying pathological mechanisms requiring further investigation. This study aimed to explore the effects of Botulinum Toxin...
BACKGROUND: The management of temporomandibular disorders (TMD) remains challenging, with its underlying pathological mechanisms requiring further investigation. This study aimed to explore the effects of Botulinum Toxin A (Botox A) on the lateral pterygoid (LP) muscle and its impact on condylar subchondral bone mass. METHODS: Rats were randomly assigned to either an experimental group (injected with Botox A) or a control group (injected with an equal volume of 0.9% normal saline). All rats were sacrificed at 2-, 4-, 8-, or 12-weeks post-injection. The right condyles were harvested and analyzed using Micro-computed tomography (CT) scanning and hematoxylin-eosin staining to evaluate changes in the condylar subchondral bone. Osteoclast activity in the subchondral bone was assessed via tartrate-resistant acid phosphatase (TRAP) staining. The activities of osteoclasts and osteoblasts in subchondral bone were detected by western blotting. RESULTS: At 2-weeks post-Botox A injection, the trabecular number (Tb.N) was significantly lower ( < 0.01). At 2- and 4-weeks, bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) were significantly lower ( < 0.05), while trabecular space (Tb.SP) and the ratio of bone surface area to bone volume (BS/BV) were significantly increased in the experimental group compared to control group ( < 0.05). At 8-weeks, BS/BV remained significantly elevated ( < 0.05), but no significant differences were observed in Tb.N, Tb.Th, BV/TV, or Tb.Sp at 8- and 12- weeks. Osteoclast numbers in the condylar subchondral bone were significantly higher in the Botox A group at 2-, 4-, and 8-weeks compared to the control group ( < 0.05). Additionally, protein expression levels of osteocalcin (OCN) and type I collagen (COL1A1) were markedly increased in the experimental group at 8- and 12-weeks ( < 0.05). CONCLUSIONS: Botox A induces a significant reduction in condylar subchondral bone mass in rats during the early post-injection period, with subsequent time-dependent recovery.
Investigating the Mechanisms of Esketamine in Treating Propofol-Induced Cognitive Impairment in Elderly Rats.
Zhang J, Xu G, Wang X … +1 more , Qiao L
Discov Med · 2025 Apr · PMID 40287805 · Publisher ↗
BACKGROUND: Common cognitive impairment in the elderly may be aggravated by the anesthetic propofol, whereas the mammalian target of rapamycin protein ()-brain-derived neurotrophic factor () pathway and autophagy regulat...
BACKGROUND: Common cognitive impairment in the elderly may be aggravated by the anesthetic propofol, whereas the mammalian target of rapamycin protein ()-brain-derived neurotrophic factor () pathway and autophagy regulation play a key role in neuroprotection. In this study, we investigated whether esketamine can improve propofol-induced cognitive impairment in aged rats by affecting these mechanisms and revealed potential new therapeutic strategies. METHODS: A propofol-induced age-related cognitive dysfunction model was used in the experiments. Behaviours were evaluated by the sugar-water preference test and the water maze, neuronal damage by Nissl staining, and neuronal apoptosis was detected by flow cytometry. Neuronal autophagy-related proteins phospho-mammalian target of rapamycin (p-mTOR), mTOR, BDNF, phospho-Unc-51 like autophagy activating kinase 1 (p-ULK1), Unc-51 like autophagy activating kinase 1 (ULK1), autophagy related 5 (ATG-5), and microtubule-associated protein 1 light chain 3-I/microtubule-associated protein 1 light chain 3-II (LC3-II/LC3-Ⅰ) were detected by western blotting (WB); immunohistochemistry was used to detect the deposition of β-amyloid (amyloid-beta, Aβ) in the hippocampal region and the positivity rate of caspase-3; postsynaptic density protein 95 (PSD95) and synapsin I (SYN1) levels were detected by WB. RESULTS: Water maze and sugar-water preference tests showed that the propofol group had longer escape latency, more platform crossings, lower platform quadrant time ratio, and reduced sugar-water preference, all improved by esketamine ( < 0.05). Nissl staining and immunohistochemistry revealed sparser neurons, darker staining, wrinkled morphology, and increased Aβ in the propofol group, all improved by esketamine ( < 0.05). WB showed increased phosphorylated Tau (p-Tau) and Aβ, higher apoptosis and caspase-3 positivity, and decreased BDNF, and ATG-5 in the propofol group, all reversed by esketamine. Propofol increased inflammatory markers and decreased SYN1, PSD95, and SYN expression, all of which were improved by esketamine ( < 0.05). CONCLUSION: By inhibiting the mTOR-BDNF pathway with esketamine, the inhibition of neuronal autophagy ultimately improves the cognitive dysfunction induced by propofol.
Sirtuin1 Promotes the Migration of Cells and Reduces the Accumulation of Extracellular Matrix in Trabecular Meshwork Cells Induced by Transform Growth Factor-β via Smads System.
Tie J, Guo J, Yuan J … +1 more , Wang J
Discov Med · 2025 Apr · PMID 40287804 · Publisher ↗
BACKGROUND: Primary open-angle glaucoma (POAG) is one of the common types of glaucoma, an eye disease that causes irreversible blindness. Fibrosis of the trabecular meshwork (TM) caused by the accumulation of extracellul...
BACKGROUND: Primary open-angle glaucoma (POAG) is one of the common types of glaucoma, an eye disease that causes irreversible blindness. Fibrosis of the trabecular meshwork (TM) caused by the accumulation of extracellular matrix (ECM) induced by transform growth factor-β (TGF-β) is closely related to high intraocular pressure (IOP). Deacetylase Sirtuin1 (Sirt1) plays an anti-oxidation and anti-fibrosis role in many diseases, including glaucoma; however, its mechanisms have not been fully revealed. In this study, we analyzed the anti-fibrotic role of Sirt1 in TM fibrosis induced by TGF-β to investigate potential mechanisms. METHODS: Transcriptome sequencing of trabecular meshwork cells (TMCs) was performed after transfection with the adenovirus-Sirt1-green fluorescent protein (Adv-Sirt1-GFP). Then, 5 ng/mL TGF-β was used to induce overexpression of ECM in TMCs . The expression of target proteins was detected by Western blot and immunofluorescence, and cytokine expression was detected by enzyme-linked immunosorbent serologic assay (ELISA). At the same time, we detected the functional changes in cell proliferation, adhesion, and migration. RESULTS: After treatment with TGF-β, we found that the accumulation of ECM was increased (fibronectin (FN), collagen I (COL I), laminin (LN), < 0.05), and the phosphorylation (activation) of Smad2/3 and the expression of Smad4 were increased ( < 0.001). The results of transcriptome sequencing suggested that Sirt1 inhibits the expression of ECM by regulating the functions of co-Smad and co-COL binding proteins, thus participating in the regulation of cell adhesion. Finally, we confirmed that: (1) Sirt1 reduced the accumulation of ECM in TMCs by inhibiting the phosphorylation of Smad2/3 ( < 0.05) and the expression of Smad4 ( < 0.05), and (2) Sirt1 decreased the adhesive ability of TMCs by reducing the secretion of integrins (integrin-α3 (ITGα3), < 0.01; integrin-β1 (ITGβ1), < 0.001) and cadherins (E-cadherin, < 0.01; N-cadherin, < 0.01), and promoted cell migration ( < 0.05). CONCLUSION: Sirt1 promotes the migration of cells and reduces the accumulation of ECM in TMCs induced by TGF-β by inhibiting the activation of Smad2/3 and the expression of Smad4.
Celastrol Targets to Induce Autophagy-Dependent Ferroptosis in Hepatocellular Carcinoma Cells.
Yan J, Xu T
Discov Med · 2025 Apr · PMID 40287803 · Publisher ↗
BACKGROUND: Celastrol has been shown to inhibit hepatocellular carcinoma (HCC) progression, but the underlying mechanism is unknown. Fanconi anemia complementation group D2 (), a ferroptosis inhibitor, promotes HCC proli...
BACKGROUND: Celastrol has been shown to inhibit hepatocellular carcinoma (HCC) progression, but the underlying mechanism is unknown. Fanconi anemia complementation group D2 (), a ferroptosis inhibitor, promotes HCC proliferation and invasion. This study aims to investigate whether Celastrol exerts its effects by targeting . METHODS: Using data from The Cancer Genome Atlas (TCGA), we identified differentially expressed genes in HCC utilizing Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). and Celastrol were analyzed for molecular docking using Autodock, which was based on geometric matching and energy matching. The correlation between and survival rate was analyzed using Kaplan-Meier's estimates by log-rank (Mantel-Cox) test. HCC cell lines (SNU-423 and SNU-387) were overexpressed or silenced with and treated with Celastrol. Autophagy and ferroptosis were evaluated by measuring oxidative stress and related markers, and cell function experiments were performed. RESULTS: High expression of was correlated with poor survival in HCC patients. Celastrol targeted , reducing its level in SNU-423 and SNU-387 cells. overexpression resulted in increased SNU-423 cell viability, migration, invasion, and tube formation ability, as well as attenuated autophagy and ferroptosis, while knockdown in SNU-387 cells showed opposite effects. Additionally, overexpression reversed the ability of Celastrol to induce autophagy and ferroptosis and to inhibit SNU-423 cell survival , while knockdown enhanced the effects of Celastrol in SNU-387 cells. CONCLUSION: Celastrol inhibits malignant behavior in HCC cells by targeting to induce autophagy-dependent ferroptosis.
Protective Role of Protocatechuic Acid in Glioma: Modulation of Cell Growth, Migration, and Pyroptosis via NLRP3/Caspase-1/GSDMD Axis.
Zhang W, Cai Y, Zheng H
Discov Med · 2025 Apr · PMID 40287802 · Publisher ↗
BACKGROUND: Glioblastoma is a common primary malignant tumor posing a serious threat to human life and health. Protocatechuic acid (PCA) is a natural phenolic compound with good anti-tumor activity. The study aimed to in...
BACKGROUND: Glioblastoma is a common primary malignant tumor posing a serious threat to human life and health. Protocatechuic acid (PCA) is a natural phenolic compound with good anti-tumor activity. The study aimed to investigate whether pyroptosis can be activated by PCA in glioma cell. METHODS: Different concentrations of PCA were used to treat glioma cell lines U87 and U251 for varying durations. Cell proliferation was quantified using the Cell Counting Kit-8 (CCK-8) assay. The Transwell chamber assay was employed to evaluate cell invasion, while cell migration was assessed via the scratch assay. Pyroptosis levels were determined through immunofluorescence staining. Additionally, the protein and mRNA expression levels of nucleotide-binding and oligomerization domain-like receptor thermal protein domain-associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (caspase-1), and gasdermin D (GSDMD) were analyzed using Western blotting and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: Intervention with PCA resulted in a significant suppression of viability, invasion and migration of glioma cells in a dose-dependent manner ( < 0.05). Additionally, the GSDMD positivity rate, as well as the protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD showed significant increases in glioma cells ( < 0.05). Further intervention with NLRP3-specific inhibitor MCC950 reversed the effects of PCA and resulted in a significant increase in cell viability and number of invading cells ( < 0.01), a significant decrease in GSDMD positivity ( < 0.01), and a significant decrease in the protein and mRNA expression levels of NLRP3, caspase-1, and GSDMD in glioma cells ( < 0.01). CONCLUSION: PCA mediates pyroptosis in glioma cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway.
Interleukins in Urological Diseases.
Akdere H, Bilir B, Kuvan HC … +1 more , Cevik G
Discov Med · 2025 Apr · PMID 40287801 · Publisher ↗
Interleukins (ILs) are a group of cytokines that regulate immune responses and inflammation, playing important roles in the pathogenesis, diagnosis, and treatment of urological diseases. This review provides an analysis...
Interleukins (ILs) are a group of cytokines that regulate immune responses and inflammation, playing important roles in the pathogenesis, diagnosis, and treatment of urological diseases. This review provides an analysis of the involvement of interleukins in bladder cancer, benign prostatic hyperplasia (BPH), renal cell carcinoma (RCC), urinary tract infections (UTIs), interstitial cystitis/bladder pain syndrome (IC/BPS), and urolithiasis. ILs regulate immune cell activity and mediate tumor progression, immune evasion, and inflammation, making them valuable biomarkers and therapeutic targets. Elevated levels of IL-6, IL-8, and IL-18 are associated with disease severity and prognosis in bladder cancer, RCC, and BPH. Additionally, IL-10 is anti-inflammatory, offering therapeutic potential in chronic inflammatory conditions such as BPH and IC/BPS. Emerging therapies targeting IL pathways, including IL-2 and IL-17 inhibitors, have shown promise in modulating immune responses and improving clinical outcomes. The diagnostic utility of urinary IL biomarkers, particularly IL-6 and IL-8, has been demonstrated in UTIs and urolithiasis. This review highlights not only the therapeutic potential of interleukins but also their integral role in the immunopathology of urological diseases, distinguishing it from previous analyses by emphasizing IL-targeted therapies to improve diagnostic and therapeutic outcomes.
Immunomodulatory Role of T Cell Immunoglobulin and Mucin Domain-3 in Cancer.
Chaudhary A, Yadav P, Chaudhary P … +2 more , Sargam S, Manna PP
Discov Med · 2025 Apr · PMID 40287800 · Publisher ↗
Immune checkpoint inhibitors are one of the most promising areas in oncoimmunology research. T cell immunoglobulin and mucin domain-3 (TIM-3) expression has been linked to the advanced stages with reduced survival in sev...
Immune checkpoint inhibitors are one of the most promising areas in oncoimmunology research. T cell immunoglobulin and mucin domain-3 (TIM-3) expression has been linked to the advanced stages with reduced survival in several types of cancer, primarily due to its association with the dysfunction in T cells. Thus, TIM-3 is an interesting target in designing advanced therapy for cancer. TIM-3 has been implicated in resistance to immunotherapy on account of its involvement in T cell exhaustion. Identifying small molecule inhibitors targeting TIM-3 with high affinity, either alone or in combination with either chemotherapy or other types of immunotherapies could significantly enhance the life span, overcoming the resistance and overall immune response in therapy. TIM-3 pathway is multidimensional in terms of canonical signaling with varied expression of immune cells and diverse ligands and modulates the immune response. This may include restoration of the functioning of killer T lymphocytes and natural killer cells (NK cells) and likely promise better results in cancer immunotherapy. In this review, we will discuss the immunomodulatory role of TIM-3 in cancer, with special emphasis on lymphoma and solid tumors, and their role in diverse immune cells in tumorigenesis and inflammation.
CAR-T Therapy for the Treatment of Colorectal Cancer.
Lecumberri A, Arasanz H, Caseda I … +6 more , Huerta AE, Castro N, Labiano I, Alsina M, Ramirez N, Vera R
Discov Med · 2025 Apr · PMID 40287799 · Publisher ↗
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Advanced CRC has a poor prognosis, with treatment primarily relying on chemotherapy combined with targeted therapies. Currently, immunotherapy bas...
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Advanced CRC has a poor prognosis, with treatment primarily relying on chemotherapy combined with targeted therapies. Currently, immunotherapy based on immune checkpoint inhibitors is reserved exclusively for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, which represent less than 10% of advanced CRC cases. Chimeric antigen receptor (CAR)-T cell therapy is a type of adoptive cell therapy involving modified T-lymphocytes engineered to express chimeric antigen receptors, enabling them to recognize surface antigens expressed by tumor cells. CAR-T cell therapy has demonstrated efficacy in treating hematological malignancies such as lymphoma, myeloma, and leukemia. However, its efficacy in solid tumors remains limited due to several limitations such as antigen heterogeneity, restricted CAR-T cell trafficking into the tumor area, and the presence of an immunosuppressive tumor microenvironment. Developing novel CAR-T cell therapies for solid tumors represents an unmet need, particularly for cases where immune checkpoint blockade is ineffective, such as CRC. Preclinical studies have shown the efficacy of various CAR-T cell models targeting a wide range of tumor-associated antigens in CRC, both and . Despite these promising results, the clinical efficacy of CAR-T cell therapy for CRC has been limited in early-phase clinical trials. Factors such as trial design or tumor characteristics, including antigen heterogeneity and the immunosuppressive microenvironment, should be considered. The development of innovative CAR-T cell models and the identification of novel antigens may improve the effectiveness of CAR-T cell therapy for CRC patients.
GPCRs With mTOR Signaling Expressed in Gut-Brain-Immune Axis-Cells Could Contribute to the Treatment of Neurodegenerative Diseases and Immune-Related Diseases.
Fukumoto A, Suga N, Nakashima M … +1 more , Matsuda S
Discov Med · 2025 Apr · PMID 40287798 · Publisher ↗
The central nervous system (CNS) and the immune system might cooperate with each other on various levels in a body. Interestingly, signaling pathways linked to several G protein-coupled receptors (GPCRs) have been shown...
The central nervous system (CNS) and the immune system might cooperate with each other on various levels in a body. Interestingly, signaling pathways linked to several G protein-coupled receptors (GPCRs) have been shown to be involved in the pathology both of CNS disorders including neurodegenerative diseases and/or immune-related diseases. Oxidative stress and inflammation are likely to contribute to cell damage and death in these disorders, which in turn could cause mitochondrial injury. Interestingly, it has been revealed that gut microbiota could play a significant role in changing the phenotype of various neuron and/or immune-related disorders. Remarkably, GPCR signaling has been recognized as a key upstream regulator for autophagy/mitophagy via the action of the mammalian/mechanistic target of rapamycin (mTOR) signaling. In addition, adjusting the composition of gut microbiota could be applied to modulate the autophagy/mitophagy by the alteration of GPCR signaling to ameliorate the mitochondrial injury. Collectively, this approach may contribute to the innovative development of promising therapeutics for neurodegenerative diseases and/or immune-related diseases. This review describes that concept, highlighting the intracellular mTOR signaling from the cell surface GPCRs within cells of Gut-brain-immune axis.
Comparative Analysis of Anterior vs Posterior Approaches in Eyelid Ptosis Repair.
Zeppieri M, Cazzato V, Surico PL … +6 more , Caputo GG, Parodi PC, D'Esposito F, Musa M, Gagliano C, Scarabosio A
Discov Med · 2025 Apr · PMID 40287797 · Publisher ↗
Eyelid ptosis, characterized by the drooping of the upper eyelid, can significantly impair vision and aesthetics. Surgical repair is often necessary, and the choice between the anterior and posterior approaches is crucia...
Eyelid ptosis, characterized by the drooping of the upper eyelid, can significantly impair vision and aesthetics. Surgical repair is often necessary, and the choice between the anterior and posterior approaches is crucial for optimal outcomes. This review compares these two techniques based on efficacy, safety, and recovery. The anterior approach, typically involving an external incision along the eyelid crease, allows direct access to the levator muscle or aponeurosis for resection or advancement. This method is particularly advantageous in cases of aponeurotic ptosis where direct visualization is often necessary. Benefits include enhanced control over eyelid height and contour, with the potential for superior cosmetic outcomes due to hidden incisions. However, the anterior approach carries a higher risk of complications such as hematoma, infection, and scarring, necessitating careful patient selection and surgical expertise. Conversely, the posterior approach, involving an internal incision through the conjunctiva, is less invasive and avoids external scars. This technique is predominantly used for mild to moderate ptosis, especially in patients with preserved levator function. It targets Müller's muscle, which is less traumatic and associated with a shorter recovery time and lower complication rates. The posterior approach is favored for its simplicity and reduced risk profile, though it offers limited visualization and may not be suitable for all ptosis types. In conclusion, both the anterior and posterior approaches to eyelid ptosis repair have distinct advantages and limitations. The choice of technique should be individualized, considering factors such as the severity of ptosis, patient anatomy, desired outcomes, and potential risks. A thorough preoperative assessment and discussion of patient expectations are essential to achieving the best surgical results.
Two Novel Variants in the LRR Domain of Causing Leukoencephalopathy: A Case Report.
Feng Z, Wu N, Shao Y … +2 more , Lin N, Shen M
Discov Med · 2025 Mar · PMID 40116107 · Publisher ↗
AIM: The NLR family pyrin domain containing 3-associated autoinflammatory disease (-AID) is a rare and heterogeneous hereditary inflammatory disorder caused by variants in the gene on chromosome 1q44. This condition enc...
AIM: The NLR family pyrin domain containing 3-associated autoinflammatory disease (-AID) is a rare and heterogeneous hereditary inflammatory disorder caused by variants in the gene on chromosome 1q44. This condition encompasses a broad spectrum of clinical phenotypes, including urticarial rash, fever, ocular disorders, hearing loss, and musculoskeletal and central nervous system (CNS) involvement. This study reports the clinical features and newly identified gene variants in two Chinese Han patients with -AID presenting with leukoencephalopathy. CASE PRESENTATION: The study includes two adult male patients aged 25 and 24 years. Both patients experienced recurrent fevers with elevated C-reactive protein levels during febrile episodes, which normalized during asymptomatic intervals. Elevated cerebrospinal fluid protein levels and magnetic resonance imaging (MRI) findings of intracranial calcification and white matter damage were observed in both cases. Genetic testing revealed novel heterozygous variants: p.L798M in Patient 1 and p.K829T in Patient 2. Both patients received treatment with adalimumab and canakinumab, resulting in significant clinical improvement. RESULTS: The clinical and genetic features of two -AID patients were characterized. Functional studies demonstrated overactivation of the NLRP3 inflammasome in these patients. CONCLUSIONS: Neurological involvement in -AID patients is variable. This study expands the clinical spectrum of CNS damage in -AID to include intracranial calcification and leukoencephalopathy. Additionally, two novel variants, L798M and K829T, were identified and associated with the disease.
Analysis of and Expression in Peripheral Blood Mononuclear Cells of Dengue-Infected Patients and Healthy Donors.
Sberna G, Lalle E, Amendola A … +7 more , Mariano A, Bordi L, Giancola ML, Mija C, Girardi E, Nicastri E, Maggi F
Discov Med · 2025 Mar · PMID 40116106 · Publisher ↗
BACKGROUND: Although evidence exists on the potential involvement of circular RNAs (circRNAs) in the pathogenesis of several viral infections, the expression levels, and the exact role that and could play during the De...
BACKGROUND: Although evidence exists on the potential involvement of circular RNAs (circRNAs) in the pathogenesis of several viral infections, the expression levels, and the exact role that and could play during the Dengue virus (DENV) infection are still unclear. These two circRNAs were identified as possible biomarkers for diagnosis and prognosis of DENV disease in peripheral blood mononuclear cells (PBMC) of Dengue-positive patients. This study aimed to evaluate the expression levels of and in DENV-infected patients and compare them with healthy donors (HD) to provide new insights into the biological significance of these two circRNAs' expression. METHODS: We examined the presence and expression levels of and in PBMC of DENV-patients throughout a period of 28 days after the DENV diagnosis. HD was used as a control group. RESULTS: Our results show different expression levels and patterns between and , both in DENV patients and HD. CONCLUSION: Possible change in the expression during DENV infection was observed, mainly at the time of diagnosis, but without a consistent pattern among patients during follow-up. Further studies are needed to clarify their expression levels and function both in Dengue-positive patients and HD.
The Correlation between GSK3β and miR-140 and its Effect on the Pathogenesis of Asthma.
Yang T, Xu C, Ding N … +4 more , Luo S, Luo L, Jin S, Chen Y
Discov Med · 2025 Mar · PMID 40116105 · Publisher ↗
BACKGROUND: MicroRNAs (miRNAs) are linked to asthma progression. In this study, we aimed to decipher the functional role of miR-140 and delineate its link to the mechanism behind the progression of asthma. METHODS: BALB/...
BACKGROUND: MicroRNAs (miRNAs) are linked to asthma progression. In this study, we aimed to decipher the functional role of miR-140 and delineate its link to the mechanism behind the progression of asthma. METHODS: BALB/c mice were divided into four groups, designated as control, asthma, Agomir negative control (NC), and Agomir group. model of asthma using transforming growth factor-beta 1 (TGF-β1)-treated 16HBE cells, and cells transfected with glycogen synthase kinase 3β (GSK3β) overexpression plasmid or Agomir miR-140. Real-time quantitative polymerase chain reaction (RT-qPCR) was to test miR-140 abundance. Hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) of lung tissues for examining their histopathological changes. Enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were to test inflammatory factors levels and cell apoptosis, respectively. B-cell lymphoma 2 (Bcl-2), GSK3β, cleaved caspase-3 and Bcl-2 associated X protein (BAX) protein levels were evaluated using Western blotting. GSK3β expression was also detected using immunohistochemistry (IHC). RNA immunoprecipitation (RIP) and dual-luciferase reporter assay were to verify the correlation between GSK3β and miR-140. RESULTS: Both the asthma mice and TGF-β1-treated 16HBE cells exhibited decreased miR-140 level and increased protein expression of GSK3β ( < 0.001). Compared with the asthma mice, overexpression of miR-140 significantly relieved airway inflammation and reduced cell apoptosis ( < 0.001). Targeted relationship existed between GSK3β and miR-140, and the overexpression of miR-140 dramatically repressed the level of GSK3β in asthma group and TGF-β1-treated 16HBE cells ( < 0.001). Nevertheless, the suppressive impacts of miR-140 overexpression were hindered by GSK3β upregulation in TGF-β1-treated 16HBE cells ( < 0.01 or < 0.001). CONCLUSIONS: miR-140 mitigates airway inflammation and represses apoptosis in asthma by targeting and regulating GSK3β.
Regulating Osteogenic Fate: How Dexamethasone Targets the CAST-CAPN1-ATP5A1 Axis in BMSCs.
Zhong G, Cen S, Zhong Z … +1 more , Teng L
Discov Med · 2025 Mar · PMID 40116104 · Publisher ↗
BACKGROUND: Osteoporosis is a common systemic metabolic disease, leading to increased bone fragility and risk of fractures. Research has shown that Adenosine triphosphate (ATP) synthase, H+transporting, mitochondrial F1...
BACKGROUND: Osteoporosis is a common systemic metabolic disease, leading to increased bone fragility and risk of fractures. Research has shown that Adenosine triphosphate (ATP) synthase, H+transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1), a crucial component in ATP production, is inhibited in dexamethasone (DEX)-induced osteoblasts. Therefore, this study aimed to investigate the molecular mechanism underlying the inhibitory impact of DEX on osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: Rat BMSCs were treated with varying concentrations of DEX for 14 days, followed by subsequent analyses. The expression levels of calpastatin (CAST), calpain 1 (CAPN1), and ATP5A1 were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analyses. Furthermore, osteogenic marker proteins and ATP activity were evaluated employing Western blotting analysis and enzyme-linked immunosorbent assay (ELISA). Moreover, to determine the regulatory role of DEX on the CAST-CAPN1 axis, overexpression plasmids for (oe-) and (oe-) were constructed. Additionally, osteogenic differentiation and ATP activity in BMSCs were analyzed using qRT-PCR, Western blotting, Alizarin Red S staining, and ELISA. RESULTS: With increasing concentrations of DEX, the expression of the CAST-CAPN1-ATP5A1 axis in BMSCs was significantly altered ( < 0.05). DEX downregulated the levels of osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin (OPN), while reducing ATP activity ( < 0.05). However, oe- partially mitigated the inhibitory effects of DEX on osteogenic differentiation and ATP activity ( < 0.05). In contrast, oe- exacerbated the effects of DEX and reversed the regulatory impact of CAST ( < 0.05). CONCLUSION: DEX inhibits osteogenic differentiation and reduces ATP activity in BMSCs by modulating the CAST-CAPN1 axis.
Study on the Application of MLPA Detection for Large Fragment Loss of Mismatch Repair Genes in Chinese HNPCC Families.
Huo M, Zhang Y, Liu H … +2 more , Du Y, Yan S
Discov Med · 2025 Mar · PMID 40116103 · Publisher ↗
BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations of human DNA mismatch repair () genes. A significant proportion of HNPCC cases are attributed to...
BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disease caused by germline mutations of human DNA mismatch repair () genes. A significant proportion of HNPCC cases are attributed to large genomic rearrangements of genes, but this finding has been less frequently reported in Chinese populations. METHODS: Array-based multiplex ligation-dependent probe amplification (array-MLPA) was employed in this study to detect genomic rearrangements of 82 probands of Chinese HNPCC families. RESULTS: According to the results, 18 probands harbored germline genomic deletions of MutL homolog 1 () and MutS homolog 2 () genes, accounting for approximately 22% (18/82) of the total subjects. Meanwhile, gene deletion occurred only in about 2.4% of the probands (2/82). The deletions of , and genes were confirmed by classic MLPA analysis, with a concordance rate of 95.5% (21/22). CONCLUSION: Array-MLPA is a highly efficient and precise method for clinical screening and diagnosis of HNPCC. By using this method, we found that the HNPCC families carry deletions of and genes, which are the major germline genomic aberrations in the studied probands. Nevertheless, the deletion of the gene is considered a rare occurrence in Chinese HNPCC families, according to our researche. Despite that, it is of clinical significance to screen and diagnose the HNPCC at the early phase by detecting the germline genomic large aberrations in genes.
CD271 Serves as a Marker for Tumor-Initiating Cells in Laryngocarcinoma.
Shen Y, Xu C, Liu X … +6 more , Zhang J, Geng F, Zhang R, Li D, Zhang B, Li X
Discov Med · 2025 Mar · PMID 40116102 · Publisher ↗
BACKGROUND: Tumor-initiating cells (TICs) play a pivotal role in the unfavorable outcomes of laryngeal tumor proliferation, recurrence, and resistance to chemoradiotherapy. This study aims to explore the expression of CD...
BACKGROUND: Tumor-initiating cells (TICs) play a pivotal role in the unfavorable outcomes of laryngeal tumor proliferation, recurrence, and resistance to chemoradiotherapy. This study aims to explore the expression of CD271 (p75 neurotrophin receptor (p75) in human laryngocarcinoma Hep2 cells and unravel its potential biological functions as a marker of laryngeal TICs. MATERIALS AND METHODS: Immunomagnetic cell sorting was utilized to separate subsets of Hep-2 cells based on high and low expression levels of CD271. Various aspects such as proliferation activity, colony formation ability, cell cycle distribution, and the expression of cancer-related proteins in each subpopulation were evaluated using immunofluorescence, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, soft agar gel assay, flow cytometry, and western blot assay. Furthermore, the tumor-forming potential of the subsets displaying high and low CD271 expression was examined through an experiment involving nude mice. The proteins associated with the phosphorylated signal transducer and activator of transcription 3 (p-STAT3)/Octamer-binding transcription factor 4 (OCT4) pathway were detected via western blot assay. RESULTS: The expression of CD133 was the highest in the CD271 high-expression group, and the expression of CD133 was the lowest in the CD271 low-expression group. Hep2 cells with high CD271 expression exhibited enhanced proliferation capacity, in contrast to those with low CD271 expression which showed reduced proliferation ( < 0.05). The CD271 high-expression group of Hep2 cells demonstrated superior clonogenic ability, a higher proportion in the S and G2/M phases of the cell cycle, and an increased sphere-forming capacity. Moreover, Hep2 cells with high CD271 expression displayed enhanced tumor formation capability in nude mice ( < 0.001). Western blot analysis indicated significantly elevated levels of specific proteins such as OCT4, Nanog Homeobox (NANOG) and p-STAT3/STAT3 in the CD271 high-expression group were significantly higher than those in the control group ( < 0.01), and the protein levels of low-expression group were significantly lower than those in the control group ( < 0.01). CONCLUSIONS: CD271 serves as a marker for TICs in Hep-2 cells, presenting a novel target for further investigation.
Structural Changes in Membrane Dynamics under the Action of Miltefosine.
Georgieva I, Apostolova S, Vukova T … +2 more , Kostadinov K, Tzoneva R
Discov Med · 2025 Mar · PMID 40116101 · Publisher ↗
BACKGROUND: Miltefosine, an alkylphosphocholine, affects lipid metabolism and cell signaling by interacting with cell membranes. In this study, we aim to demonstrate the effect of miltefosine (hexadecylphosphocholine (He...
BACKGROUND: Miltefosine, an alkylphosphocholine, affects lipid metabolism and cell signaling by interacting with cell membranes. In this study, we aim to demonstrate the effect of miltefosine (hexadecylphosphocholine (HePC)) on the alterations of the membrane lipid content of human lung adenocarcinoma (A549) cells and normal human umbilical vein endothelial cells (HUVECs) in respect to the reduction of their membrane fluidity and metastatic potential of the cancer cells. METHODS: To study lateral diffusion in cell membranes, we employed membrane labeling with fusogenic liposomes followed by fluorescence recovery after photobleaching (FRAP) analysis. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay; total cholesterol and sphingomyelin were measured using commercially available kits. RESULTS: Miltefosine inhibited cell growth and increased the total cholesterol in both cell lines ( < 0.05 for HUVEC and < 0.01 for A549). Sphingomyelin levels were not significantly altered in A549 cells, but in HUVECs HePC caused a decrease in sphingomyelin ( < 0.05). Miltefosine treatment of A549 cells reduced the membrane diffusion coefficient ( < 0.001), which was associated with an increased half-time of fluorescent recovery ( < 0.05) measured by FRAP. These changes reflect a significant reduction in membrane fluidity in the cancer cells. In contrast, miltefosine induced a milder response in HUVECs, attenuating the diffusion coefficient ( < 0.05) but not affecting the half-time of fluorescent recovery. As a result, the reduction in membrane fluidity in HUVECs was less pronounced. CONCLUSION: Miltefosine induces a decrease in membrane fluidity of cancer cells, and this effect was related to decreased cell viability and total cholesterol levels. Miltefosine may be an effective antitumor agent and has great potential as an adjuvant therapy in the future.
Anti-Inflammatory Effect of Calycosin on Hypoxia-Induced Retinal Pigment Epithelium Cells.
Zhu T, Wang B, Huang W … +2 more , Zhang H, Cai R
Discov Med · 2025 Mar · PMID 40116100 · Publisher ↗
BACKGROUND: Calycosin is thought to have anti-cancer and anti-inflammatory characteristics; however, more research is needed to determine how it impacts retinal pigment epithelium (RPE) cells. This study aims to explore...
BACKGROUND: Calycosin is thought to have anti-cancer and anti-inflammatory characteristics; however, more research is needed to determine how it impacts retinal pigment epithelium (RPE) cells. This study aims to explore the effects of calycosin on RPE cells under hypoxia. METHODS: Experimental hypoxia was induced by treating RPE cells with cobalt chloride for 2, 4, and 6 h. To investigate the effect of calycosin on RPE cells under hypoxia, RPE cells were treated with calycosin and cobalt chloride (CoCl). Cells were assessed for viability (Cell Counting Kit-8 assay) and apoptosis (flow cytometry). Inflammatory cytokines (enzyme-linked immunosorbent assay) and genes or proteins related to apoptosis and the hypoxia-inducible factor-1α ()/nuclear factor-κB () axis (quantitative real-time polymerase chain reaction and western blot) were measured. RESULTS: Under hypoxic conditions, RPE cells showed reduced viability but increased levels of inflammation and apoptosis. The pathway was activated, and , apoptosis/ pathway-related proteins (cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP); phosphorylated-p65 (p-p65), p-p65/p65), and inflammatory cytokines (interleukin-6 (IL-6) and interleukin-8 (IL-8)) were upregulated ( < 0.001). Calycosin weakened the effects of hypoxia on RPE cells ( < 0.05). CONCLUSION: Calycosin inhibits the / axis and protects RPE cells from hypoxia-induced inflammation and apoptosis.
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