A narrative review on therapeutic potential of naringenin in colorectal cancer: Focusing on molecular and biochemical processes.

Colorectal cancer (CRC) is a common and highly metastatic cancer affecting people worldwide. Drug resistance and unwanted side effects are some of the limitations of current treatments for CRC. Naringenin (NAR) is a naturally occurring compound found in abundance in various citrus fruits such as oranges, grapefruits, and tomatoes. It possesses a diverse range of pharmacological and biological properties that are beneficial for human health. Numerous studies have highlighted its antioxidant, anticancer, and anti-inflammatory activities, making it a subject of interest in scientific research. This review provides a comprehensive overview of the effects of NAR on CRC. The study's findings indicated that NAR: (1) interacts with estrogen receptors, (2) regulates the expression of genes related to the p53 signaling pathway, (3) promotes apoptosis by increasing the expression of proapoptotic genes (Bax, caspase9, and p53) and downregulation of the antiapoptotic gene Bcl2, (4) inhibits the activity of enzymes involved in cell survival and proliferation, (5) decreases cyclin D1 levels, (6) reduces the expression of cyclin-dependent kinases (Cdk4, Cdk6, and Cdk7) and antiapoptotic genes (Bcl2, x-IAP, and c-IAP-2) in CRC cells. In vitro CDK2 binding assay was also performed, showing that the NAR derivatives had better inhibitory activities on CDK2 than NAR. Based on the findings of this study, NAR is a potential therapeutic agent for CRC. Additional pharmacology and pharmacokinetics studies are required to fully elucidate the mechanisms of action of NAR and establish the most suitable dose for subsequent clinical investigations.

Missile embolism from pulmonary vein to left ventricle: report of a case.

Missile embolization is rare in penetrating trauma, occurring in 0.3% of cases. Bullet embolism into the left ventricle is less frequent, with few instances described in the literature. This paper describes an instance of left ventricular bullet embolism from the pulmonary venous system following gunshot chest trauma. A 7-year-old boy sustained a gunshot wound to his chest during an assault accident. Despite thoracic pain, he remained conscious and exhibited vital signs. A CXR and CT scan revealed a bullet in the left mediastinum. A left thoracotomy was performed to remove blood and clots from the pericardium. The patient was sent to a tertiary referral hospital for further investigation. The patient underwent elective surgery to remove the foreign body from inside the heart. The procedure involved a partial thymectomy and pericardial opening, and the patient was released from medical care after 14 days. After 6 months, there were no signs or symptoms of cardiothoracic infection or evidence of mitral valve regurgitation in echocardiography.

Brain MRI findings in neurologically symptomatic COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been associated with nervous system involvement, with more than one-third of COVID-19 patients experiencing neurological manifestations. Utilizing a systematic review, this study aims to summarize brain MRI findings in COVID-19 patients presenting with neurological symptoms. METHODS: Systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. The electronic databases of PubMed/MEDLINE, Embase, Scopus, and Web of Science were systematically searched for literature addressing brain MRI findings in COVID-19 patients with neurological symptoms. RESULTS: 25 publications containing a total number of 3118 COVID-19 patients with neurological symptoms who underwent MRI were included. The most common MRI findings and the respective pooled incidences in decreasing order were acute/subacute infarct (22%), olfactory bulb abnormalities (22%), white matter abnormalities (20%), cerebral microbleeds (17%), grey matter abnormalities (12%), leptomeningeal enhancement (10%), ADEM (Acute Disseminated Encephalomyelitis) or ADEM-like lesions (10%), non-traumatic ICH (10%), cranial neuropathy (8%), cortical gray matter signal changes compatible with encephalitis (8%), basal ganglia abnormalities (5%), PRES (Posterior Reversible Encephalopathy Syndrome) (3%), hypoxic-ischemic lesions (4%), venous thrombosis (2%), and cytotoxic lesions of the corpus callosum (2%). CONCLUSION: The present study revealed that a considerable proportion of patients with COVID-19 might harbor neurological abnormalities detectable by MRI. Among various findings, the most common MRI alterations are acute/subacute infarction, olfactory bulb abnormalities, white matter abnormalities, and cerebral microbleeds.

Adenoid 'ameloblastoma': Clinicopathological description of 4 additional BRAF-negative cases.

OBJECTIVE: Adenoid ameloblastoma (AA) is an epithelial odontogenic tumor that was recognized as a separate entity in the last odontogenic classification of WHO in 2022. The etiology is unknown, and the pathogenesis remains controversial. The objective of this study is to contribute the clinicopathological features of 4 additional BRAF-negative cases to the existing literature, aiming to enhance the molecular understanding of this unique tumor in the forthcoming classification. MATERIALS AND METHODS: This study consists of a case series of four patients diagnosed with AA. The patients' demographic and clinical information were collected from the universities' medical achieves. Histopathologically, all cases were reexamined according to the latest update of the WHO odontogenic tumor classification. In addition to H&E and immunohistochemical stains, cytogenetics was also evaluated. RESULTS: Well-defined unilocular radiolucent lesions were observed in all cases. Ameloblastoma-like components exhibited reserved nuclear polarity, suprabasal stellate reticulum-like epithelium, duct-like structure, whorls/morules, and cribriform architecture were common features. Variable immunoreactivity to CK7, CK19, CK14, p63, and p40 were determined, and proliferative activity was greater than 15%. The BRAF molecular study revealed no mutations. CONCLUSIONS: When diagnosing AA, the essential histopathological characteristics must be rigorously applied, and a significant portion of the lesion should contain these features. Additionally, despite limited molecular data, since the BRAF mutation commonly observed in ameloblastomas is not present in the majority of AA cases, we propose changing the term "ameloblastoma" to "ameloblastic" and referring to it as "adenoid ameloblastic tumor" in the forthcoming classification.

Acute Necrotizing Encephalopathy in Adult Patients With COVID-19: A Systematic Review of Case Reports and Case Series.

BACKGROUND AND PURPOSE: Acute necrotizing encephalopathy (ANE) is a rare neurological disorder that is often associated with viral infections. Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a few COVID-19-associated ANE cases have been reported. Since very little is known about ANE, the present study aimed to determine the clinical, biochemical, and radiological characteristics of affected patients. METHODS: A search was conducted on PubMed, Scopus, Embase, and Web of Science databases for articles published up to August 30, 2022 using relevant keywords. Case reports and series in the English language that reported ANE in adult patients with COVID-19 confirmed by reverse transcription polymerase chain reaction were included in this study. Data on the demographic, clinical, laboratory, and radiological characteristics of patients were extracted and analyzed using the SPSS software (version 26). RESULTS: The study included 30 patients (18 males) with COVID-19 and ANE who were aged 49.87±18.68 years (mean±standard deviation). Fever was the most-prevalent symptom at presentation (66.7%). Elevated C-reactive protein was observed in the laboratory assessments of 13 patients. Computed tomography and magnetic resonance imaging were the most-common radiological modalities used for brain assessments. The most commonly prescribed medications were methylprednisolone (30%) and remdesivir (26.7%). Sixteen patients died prior to discharge. CONCLUSIONS: The diagnosis of COVID-19-associated ANE requires a thorough knowledge of the disease. Since the clinical presentations of ANE are neither sensitive nor specific, further laboratory and brain radiological evaluations will be needed to confirm the diagnosis. The suspicion of ANE should be raised among patients with COVID-19 who present with progressive neurological symptoms.

A fragment-based drug discovery developed on ciclopirox for inhibition of Hepatitis B virus core protein: An in silico study.

The Hepatitis B virus (HBV) core protein is an attractive target for preventing capsid assembly and viral replication. Drug repurposing strategies have introduced several drugs targeting HBV core protein. This study used a fragment-based drug discovery (FBDD) approach to reconstruct a repurposed core protein inhibitor to some novel antiviral derivatives. Auto Core Fragment in silico Screening (ACFIS) server was used for deconstruction-reconstruction of Ciclopirox in complex with HBV core protein. The Ciclopirox derivatives were ranked based on their free energy of binding (ΔGB). A quantitative structure affinity relationship (QSAR) was established on the Ciclopirox derivatives. The model was validated by a Ciclopirox-property-matched decoy set. A principal component analysis (PCA) was also assessed to define the relationship of the predictive variable of the QSAR model. 24-derivatives with a ΔGB (-16.56±1.46 Kcal.mol-1) more than Ciclopirox was highlighted. A QSAR model with a predictive power of 88.99% (F-statistics = 9025.78, corrected df(25), Pr > F = 0.0001) was developed by four predictive descriptors (ATS1p, nCs, Hy, F08[C-C]). The model validation showed no predictive power for the decoy set (Q2 = 0). No significant correlation was observed between predictors. By directly attaching to the core protein carboxyl-terminal domain, Ciclopirox derivatives may be able to suppress HBV virus assembly and subsequent viral replication inhibition. Hydrophobic residue Phe23 is a critical amino acid in the ligand binding domain. These ligands share the same physicochemical properties that lead to the development of a robust QSAR mode. The same strategy may also be used for future drug discovery of viral inhibitors.

Comparable Outcomes of Pre- Versus Post-Tyrosine Kinase Inhibitor Era Treatment in Chronic Myeloid Leukemia: A Retrospective Cohort Study With Long-term Follow-up.

Imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was introduced after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with chronic myeloid leukemia (CML). However, the long-term effects of allo-HSCT in chronic phase CML patients are mostly unknown. We retrospectively analyzed the outcomes of 204 patients with sibling donors who received peripheral stem cells and underwent allo-HSCT of chronic phase I (CP1) in the pre- and post-TKI era at Shariati Hospital in Tehran, Iran, from 1998 to 2017 and followed up till the end of 2021. The median follow-up time for all patients was 8.7 (SD = 0.54) years. Fifteen-year overall survival (OS), disease-free survival (DFS), graft-versus-host disease-free relapse-free survival (GRFS), relapse, and non-relapse mortality (NRM) incidence were 65.70%, 57.83%, 17.56%, 13.17%, and 28.98%, respectively. Using multivariable analyses, the only risk factor increasing the hazard of death was the time between diagnosis to allo-HSCT greater than 1 year compared to this time less than 1 year by 74% [hazard ratio (HR) = 1.74, P = 0.039]. Also, age is a significant risk factor for DFS (HR = 1.03, P = 0.031). Our findings suggested that allo-HSCT is still an important treatment option for CP1 patients, especially those resistant to TKI treatment. TKI consumption can have a desirable effect on NRM after allo-HSCT for CP1 CML.