A paradigm shift in cancer research based on integrative multi-omics approaches: glutaminase serves as a pioneering cuproptosis-related gene in pan-cancer.

BACKGROUND: Cuproptosis is a newly identified form of unprogrammed cell death. As a pivotal metabolic regulator, glutaminase (GLS) has recently been discovered to be linked to cuproptosis. Despite this discovery, the oncogenic functions and mechanisms of GLS in various cancers are still not fully understood. METHODS: In this study, a comprehensive omics analysis was performed to investigate the differential expression levels, diagnostic and prognostic potential, correlation with tumor immune infiltration, genetic alterations, and drug sensitivity of GLS across multiple malignancies. RESULTS: Our findings revealed unique expression patterns of GLS across various cancer types and molecular subtypes of carcinomas, underscoring its pivotal role primarily in energy and nutrition metabolism. Additionally, GLS showed remarkable diagnostic and prognostic performance in specific cancers, suggesting its potential as a promising biomarker for cancer detection and prognosis. Furthermore, we focused on uterine corpus endometrial carcinoma (UCEC) and developed a novel prognostic model associated with GLS, indicating a close correlation between GLS and UCEC. Moreover, our exploration into immune infiltration, genetic heterogeneity, tumor stemness, and drug sensitivity provided novel insights and directions for future research and laid the foundation for high-quality verification. CONCLUSION: Collectively, our study is the first comprehensive investigation of the biological and clinical significance of GLS in pan-cancer. In our study, GLS was identified as a promising biomarker for UCEC, providing valuable evidence and a potential target for anti-tumor therapy. Overall, our findings shed light on the multifaceted functions of GLS in cancer and offer new avenues for further research.

Doxycycline Suppresses Vasculogenic Mimicry in Human Pterygium Fibroblasts.

PURPOSE: To explore the effect of doxycycline on vasculogenic mimicry (VM) formation and the potential mechanism in human pterygium fibroblasts in order to find novel targets for pterygium therapy. METHODS: First, we demonstrate the existence of VM in 73 pterygium specimens by CD31 and periodic acid Schiff (PAS) dual staining. Then we used cell counting kit-8, clone formation assay and flow cytometry to prove the inhibitory effect of doxycycline on cell proliferation and apoptosis. The VM formation was evaluated through wound healing assay, cell transwell assay and three-dimensional cell culture combined with PAS staining. Finally, we used Western blot to testify the correlation of the VM and the factors in protein level preliminarily. RESULTS: Our results showed that VM existed in human pterygium specimens exactly. Otherwise, in human pterygium fibroblasts, doxycycline induced a dose-dependent inhibitory effect on cell proliferation and apoptosis induction. Besides, doxycycline significantly suppressed vasculogenic mimicry tube formation, cell migration and invasion. Furthermore, doxycycline impaired the expression of MMP-9, MMP-2 and VEGF which may related to pterygium VM formation. CONCLUSIONS: Doxycycline decelerated pterygium progression might be through inhibiting VM formation according to the downregulation of MMP-9, MMP-2 and VEGF, which may provide the basis of further studies involving doxycycline for pterygium treatment.

I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis.

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A) regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I(2)(PP2A) counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis.

[Pathological study of mycobacterium abscessus keratitis].

OBJECTIVE: To characterize the cytopathology, histopathology, immunohistochemistry and ultrastructural organization features of Mycobacterium abscessus keratitis. METHODS: This retrospective case report included six cases with the lesions tissues scraped from acute phase of mycobacterium abscessus keratitis after corneal foreign body removal. Among the 6 scrapings, 4 were tested for Ziehl-Neelsen acid-fast staining and 3 were examined by transmission electron microscopy (TEM). The corneal tissues of 2 cases in chronic phase of the disease were collected during keratoplasty and were examined by pathological examination including hematoxylin-eosin (HE) staining, acid-fast staining, immunohistostaining and TEM. RESULTS: A single or fascicular red bacilli were observed after acid-fast staining in the four cases of corneal scrapings. The smear samples contained a large number of neutrophils and necrotic corneal epithelium and stroma tissue accompanying with a large number of mycobacteria that were positive for acid-fast staining scattered in and out of inflammatory cells. The corneal buttons obtained at keratoplasty in the 2 patients demonstrated corneal epithelial hyperplasia, stroma degeneration, necrosis and exelcosis, neutrophil and lymphocyte infiltration, neovascularization and fibrous hyperplasia, but no positive mycobacteria by Ziehl-Neelsen acid-fast staining. There were no CD4(+) or CD8(+) cells from immunohistochemistry examination. TEM of the corneal scrapings of the 3 cases showed phagocytosis of mycobacterium abscessus in mononuclear macrophage or neutrophils, inclusion compounds of small vacuoles and metachromatic granules in the thallium. TEM of corneal buttons of 2 cases showed slender rod-shaped mycobacteria with several to dozens of finely ground particles with high electron-dense, but no cell wall (L-form) or inclusion compounds. CONCLUSIONS: Mycobacterium abscessus keratitis presents acute purulent inflammatory changes in early stage and advances to chronic and non-specificity inflammation changes in late stage. L-formed mycobacterium abscessus make the disease protraction.

[The diagnosis and treatment of rapidly growing non-tuberculous mycobacterial keratitis].

OBJECTIVE: To study the clinical features, diagnosis and treatment of non-tuberculous mycobacterial keratitis (NTMK). METHODS: It was retrospective case series study. Twelve eyes in 12 patients with NTMK following corneal foreign body trauma in 2007 were studied retrospectively including the case histories, clinical findings, laboratory examinations, diagnosis, treatment and prognosis. The main laboratory examination included corneal scrapings by culturing, polymerase chain reaction (PCR) and transmission electron microscopy (TEM), corneal lesions by histopathologic examinations and TEM. The patients received local and systemic antibiotics therapy, lesion cleaning followed by cauterization with tincture of iodine (5%) and (or) keratoplasty. RESULTS: All cases had a history of corneal trauma, there was corneal metallic foreign body removal at one hospital in 11 cases, corneal reed trauma in 1 case. The characteristic signs involved grayish-blue crystalloid keratopathy, multifocal infiltrates, satellites, radical form changes in the Descemet's membrane. The results of laboratory examinations of the scrapings of the cornea infection were as follows: all cultures (12/12) were positive for rapidly growing mycobacteria, and isolates from 5 patients were all diagnosed as mycobacterium chelonae subspecies abscess; acid-fast staining revealed positive bacilli in all the 4 patients; seven of 8 patients were positive for bacterium by PCR. Transmission electron microscopy in all the 3 specimens showed many slender rod-shaped or short coarse-shaped bacteria which were phagocytized by monocytes, and some necrotic tissue. Infections in 10 eyes were resolved by combined treatment regimen including a combination of antimicrobial agents (amikacin, rifampin, gatifloxacin, ciprofloxacin, azithromycin and/or ofloxacin, etc.) and local lesion cleaning followed by cauterization with 5% tincture of iodine within 2-5 months; two cases resolved by keratoplasty which poorly responded to antibiotic therapy for 6 months. CONCLUSIONS: NTMK is a rare, recalcitrant opportunistic infection which can occur in an epidemic fashion following corneal foreign body trauma. The diagnosis of NTMK is difficult, and may easily be misdiagnosed as fungal keratitis. Acid-fast staining, TEM, especially bacterial culture can help to obtain definitive diagnosis. NTMK has a long response period to medical management. The majority of patients can be cured by local and systemic antibiotics therapy, and the recalcitrant infections could be resolved by keratoplasty.

[A cross-sectional survey of blindness and low vision among adults aged 60 years and above in Xinchengqiao Blocks, Nantong].

OBJECTIVE: To investigate the prevalence and causes of blindness and low vision among adults aged > or = 60 years in the urban population of Nantong. METHODS: Cluster sampling was used to select 8 from 14 communities in Xinchengqiao Blocks, in which all individuals aged > or = 60 years were visited. The visual acuity without correction and the presenting acuity with the participants' habitual distance correction were measured separately for each eye. In individuals with visual acuity less than 0.6, pinhole visual acuity was tested with pinhole spectacle. External eye, anterior segment and ocular fundus were examined by the ophthalmologist using a slit lamp-microscope and direct ophthalmoscopy. The survey was preceded by a pilot study. RESULTS: Of 3352 enumerated subjects, 3040 individuals participated in this survey (90.69% response rate). According to pinhole visual acuity and World Health Organization (WHO) visual impairment criterion (blindness: less than 0.05 in the better eye; low vision: less than 0.3 to 0.05 in the better eye), the prevalence of blindness and low vision was 1.35% and 1.84% respectively. The prevalence of blindness and low vision for females were 1.92% and 2.33%, respectively, which were differenced from that in males (0.66% and 1.24%, respectively). The prevalence of blindness and low vision increased with age. The survey showed that the most important cause leading to blindness and low vision was cataract. According to the presenting visual acuity and visual impairment criterion (blindness: less than 0.1 in both eyes), the prevalence of blindness and visual impairment was 1.58% and 13.59%, respectively, 2.10% and 15.98% in females and 0.95% and 10.66% in males, respectively. The prevalence of blindness and visual impairment was raised with increasing age. Cataract was also the leading cause for blindness. CONCLUSIONS: The prevalence of blindness in the Nantong area was lower than that in northern, southern and western China. Females and illiteracy were more likely to have blindness and low vision than that of males and literate. The leading causes of blindness in Nantong are, in descending sequence, cataract, ocular fundus diseases, ametropia and corneal scar/opacity.