Retinal Structural and Vascular Changes in Patients with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Retinal microvascular anomalies have been identified in patients with cardiovascular conditions such as arterial hypertension, diabetes mellitus, and carotid artery disease. We conducted a systematic review and meta-analysis (PROSPERO registration number CRD42024506589) to explore the potential of retinal vasculature as a biomarker for diagnosis and monitoring of patients with coronary artery disease (CAD) through optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). METHODS: We systematically examined original articles in the Pubmed, Embase, and Web of Science databases from their inception up to November 2023, comparing retinal microvascular features between patients with CAD and control groups. Studies were included if they reported sample mean with standard deviation or median with range and/or interquartile range (which were computed into mean and standard deviation). Review Manager 5.4 (The Cochrane Collaboration, 2020) software was used to calculate the pooled effect size with weighted mean difference and 95% confidence intervals (CI) by random-effects inverse variance method. RESULTS: Eleven studies meeting the inclusion criteria were incorporated into the meta-analysis. The findings indicated a significant decrease in the retinal nerve fiber layer (WMD -3.11 [-6.06, -0.16]), subfoveal choroid (WMD -58.79 [-64.65, -52.93]), and overall retinal thickness (WMD -4.61 [-7.05, -2.17]) among patients with CAD compared to controls (p < 0.05). Furthermore, vascular macular density was notably lower in CAD patients, particularly in the superficial capillary plexus (foveal vessel density WMD -2.19 [-3.02, -1.135], p < 0.0001). Additionally, the foveal avascular zone area was statistically larger in CAD patients compared to the control group (WMD 52.73 [8.79, 96.67], p = 0.02). Heterogeneity was significant (I2 > 50%) for most features except for subfoveal choroid thickness, retina thickness, and superficial foveal vessel density. CONCLUSION: The current meta-analysis suggests that retinal vascularization could function as a noninvasive biomarker, providing additional insights beyond standard routine examinations for assessing dysfunction in coronary arteries.

Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania.

Mutations in RAS, BRAF, PIK3CA, and TP53 are well-established genetic abnormalities in metastatic colorectal cancer (mCRC). However, limited information is available for patients from Eastern Europe, including Romania. In this retrospective analysis, we investigated 104 mCRC patients from the Northeastern region of Romania to determine the frequency, distribution, coexistence, and clinicopathological and molecular correlations of these mutations. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). Patients with KRAS mutant tumors and wild-type TP53 genotype were found to have no personal history of gastrointestinal cancer (p = 0.02, p = 0.007). KRAS mutations in exon 3 were associated with the female gender (p = 0.02) and the absence of lymph node invasion (p = 0.02). PIK3CA mutations were linked to the absence of lymph node invasion (p = 0.006). TP53 mutations were associated with KRAS mutations in exon 2 (p = 0.006), ulcerated histopathologic type (p = 0.04), and G2 differentiation (p = 0.01). It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations.

Breast Sarcomas-How Different Are They from Breast Carcinomas? Clinical, Pathological, Imaging and Treatment Insights.

Breast sarcoma (BS) is a very rare and poorly studied condition. This has led to a lack of studies with a high level of evidence and to low efficacy of current clinical management protocols. Here we present our experience in treating this disease in the form of a retrospective case series study including discussion of clinical, imaging, and pathological features and treatment. We also compare the main clinical and biological features of six cases of BS (phyllodes tumors were excluded) with a cohort of 184 patients with unilateral breast carcinoma (BC) from a previous study performed at our institution. Patients with BS were diagnosed at a younger age, presented no evidence of lymph node invasion or distant metastases, had no multiple or bilateral lesions, and underwent a shorter length of hospital stay versus the breast carcinoma group. Where recommended, adjuvant chemotherapy consisted of an anthracycline-containing regimen, and adjuvant external radiotherapy was delivered in doses of 50 Gy. The comparison data obtained from our BS cases and the ones with BC revealed differences in diagnosis and treatment. A correct pathological diagnosis of breast sarcoma is essential for the right therapeutic approach. We still have more to learn about this entity, but our case series could add value to existing knowledge in a meta-analysis study.

Structural insights into p300 regulation and acetylation-dependent genome organisation.

Histone modifications are deposited by chromatin modifying enzymes and read out by proteins that recognize the modified state. BRD4-NUT is an oncogenic fusion protein of the acetyl lysine reader BRD4 that binds to the acetylase p300 and enables formation of long-range intra- and interchromosomal interactions. We here examine how acetylation reading and writing enable formation of such interactions. We show that NUT contains an acidic transcriptional activation domain that binds to the TAZ2 domain of p300. We use NMR to investigate the structure of the complex and found that the TAZ2 domain has an autoinhibitory role for p300. NUT-TAZ2 interaction or mutations found in cancer that interfere with autoinhibition by TAZ2 allosterically activate p300. p300 activation results in a self-organizing, acetylation-dependent feed-forward reaction that enables long-range interactions by bromodomain multivalent acetyl-lysine binding. We discuss the implications for chromatin organisation, gene regulation and dysregulation in disease.

Hybrid Management of an Aortobronchial Fistula after Patch Aortoplasty for Aortic Coarctation in a Patient with SARS-CoV-2 Pneumonia: Case Report and Review of the Literature.

Aortobronchial fistula is a rare cause of repeated hemoptysis and a potentially fatal condition if left untreated. We present the case of a 40-year-old man with repeated hemoptysis, excessive cough, and epistaxis ongoing for several days after SARS-CoV-2 pneumonia diagnosis. The patient had a history of patch aortoplasty for aortic coarctation and aortic valve replacement with a mechanical valve for aortic insufficiency due to bicuspid aortic valve at the age of 24. Computed tomography scan performed at presentation revealed a severely dilated ascending aorta, a thoracic aorta pseudoaneurysm at the site of the former coarctation, an aortobronchial fistula suggested by the thickened left lower lobe apical segmental bronchus in contact with the pseudoaneurysm and signs of alveolar hemorrhage in the respective segment. The patient was treated with thoracic endovascular aneurysm repair (TEVAR) after prior hemi-aortic arch debranching and transposition of the left common carotid artery and subclavian artery through a closed-chest surgical approach. Our case report together with a systematic review of the literature highlight the importance of both considering an aortobronchial fistula in the differential diagnosis of hemoptysis in patients with prior history of thoracic aorta surgical intervention, regardless of associated pathology, and of taking into account endovascular and hybrid techniques as an alternative to open surgical repair, which carries a high risk of morbidity and mortality.

CG7379 and ING1 suppress cancer cell invasion by maintaining cell-cell junction integrity.

Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage, oncogene-induced senescence and apoptosis. Recent work suggests a possible role for ING1 in cancer cell invasion and metastasis, but the molecular mechanism underlying this observation is lacking. Our results show that reduced expression of CG7379 promotes invasion in vivo in Drosophila, reduces the junctional localization of several adherens and septate junction components, and severely disrupts cell-cell junction architecture. Similarly, ING1 knockdown significantly enhances invasion in vitro and disrupts E-cadherin distribution at cell-cell junctions. A transcriptome analysis reveals that loss of ING1 affects the expression of several junctional and cytoskeletal modulators, confirming ING1 as an invasion suppressor and a key regulator of cell-cell junction integrity.

A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion.

Metastasis is the leading cause of death for patients with cancer. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumor growth toward malignancy. Advances in genome characterization technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However, the difficulty in evaluating whether these candidates drive tumor progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumors with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumor progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, whose loss of function either promotes individual or collective cell invasion, depending on the severity of effect on cohesin complex function.

The multifarious regulation of the apical junctional complex.

Epithelial cells form highly organized polarized sheets with characteristic cell morphologies and tissue architecture. Cell-cell adhesion and intercellular communication are prerequisites of such cohesive sheets of cells, and cell connectivity is mediated through several junctional assemblies, namely desmosomes, adherens, tight and gap junctions. These cell-cell junctions form signalling hubs that not only mediate cell-cell adhesion but impact on multiple aspects of cell behaviour, helping to coordinate epithelial cell shape, polarity and function. This review will focus on the tight and adherens junctions, constituents of the apical junctional complex, and aims to provide a comprehensive overview of the complex signalling that underlies junction assembly, integrity and plasticity.

Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinoma in vivo.

The antitumor efficacy of 5-fluorouracil (5-FU) in advanced colorectal cancer (CRC) is hindered not only by the low therapeutic index, but also by tumor cell resistance to this cytotoxic drug. Therefore, to enhance the 5-FU antitumor activity, the present research used a novel tumor-targeted therapy based on the co-administration of 5-FU encapsulated in long-circulating liposomes (LCL-5-FU) together with liposomal prednisolone phosphate (LCL-PLP), a formulation with known anti-angiogenic actions on C26 murine colon carcinoma cells. Thus, we assessed the in vivo effects of the combined liposomal drug therapy on C26 carcinoma growth as well as on the production of molecular markers with key roles in tumor development such as angiogenic, inflammatory, and oxidative stress molecules. To get further insight into the polarization state of tumor microenvironment after the treatment, we determined the IL-10/IL-12p70 ratio in tumors. Our results showed that combined liposomal drug therapy inhibited almost totally tumor growth and was superior as antitumor activity to both single liposomal drug therapies tested. The antitumor efficacy of the combined therapy was mainly related to the anti-angiogenic and anti-inflammatory actions on C26 carcinoma milieu, being favored by its controlling effect on intratumor oxidative stress and the skewing of polarization of tumor microenvironmental cells toward their antineoplastic phenotypes. Thus, our study unveils a promising treatment strategy for CRC that should be furthermore considered.