Targeted EGFR Nanotherapy in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Despite advances in treatment, the prognosis remains poor, highlighting the need for novel therapeutic strategies. The present review explores the potential of targeted epidermal growth factor receptor (EGFR) nanotherapy as an alternative treatment for NSCLC, showing that EGFR-targeted nanoparticles are efficiently taken up by NSCLC cells, leading to a significant reduction in tumor growth in mouse models. Consequently, we suggest that targeted EGFR nanotherapy could be an innovative treatment strategy for NSCLC; however, further studies are needed to optimize the nanoparticles and evaluate their safety and efficacy in clinical settings and human trials.

Dendrimers: Advancements and Potential Applications in Cancer Diagnosis and Treatment-An Overview.

Cancer is a leading cause of death worldwide, and the main treatment methods for this condition are surgery, chemotherapy, and radiotherapy. These treatment methods are invasive and can cause severe adverse reactions among organisms, so nanomaterials are increasingly used as structures for anticancer therapies. Dendrimers are a type of nanomaterial with unique properties, and their production can be controlled to obtain compounds with the desired characteristics. These polymeric molecules are used in cancer diagnosis and treatment through the targeted distribution of some pharmacological substances. Dendrimers have the ability to fulfill several objectives in anticancer therapy simultaneously, such as targeting tumor cells so that healthy tissue is not affected, controlling the release of anticancer agents in the tumor microenvironment, and combining anticancer strategies based on the administration of anticancer molecules to potentiate their effect through photothermal therapy or photodynamic therapy. The purpose of this review is to summarize and highlight the possible uses of dendrimers regarding the diagnosis and treatment of oncological conditions.

Antidiabetic Treatment before Hospitalization and Admission Parameters in Patients with Type 2 Diabetes, Obesity, and SARS-CoV-2 Viral Infection.

BACKGROUND: SARS-CoV-2 viral infection is a current and important topic for patients with comorbidities of type 2 diabetes and obesity, associated with increased risk of mortality and morbidity. This study aims to analyze, compare and describe admission parameters in patients with type 2 diabetes, obesity, and SARS-CoV-2 infection based on whether they received insulin therapy before hospital admission. METHODS: Our study enrolled patients diagnosed with type 2 diabetes, obesity, and SARS-CoV-2 viral infection, 81 patients without insulin treatment before hospital admission, and 81 patients with insulin at "Gavril Curteanu" Municipal Clinical Hospital of Oradea, Romania, between August 2020 and March 2022. RT-PCR/rapid antigen tests were used for detecting SARS-CoV-2 viral infection. RESULTS: The severe form of COVID-19 was found in 66% of all patients (65% in the group without insulin and 67% in the group with insulin). Oxygen saturation at the time of hospital admission was greater or equal to 90% in 62% of all patients. The most associated comorbidities we founded in this study were: hypertension in 75% of all patients (grade two hypertension 63% in the group without insulin and 64% in the group with insulin), ischemic heart disease in 35% of patients (25% in the group without insulin and 44% in the group with insulin, n = 0.008), heart failure in 9.3% of all patients (8.6% in the group without insulin and 10% in the group with insulin). CRP and procalcitonin are increased in both groups at hospital admission, with a slightly higher trend in the group with insulin therapy before hospital admission. We found that 56% of patients in the group with insulin treatment were with uncontrolled diabetes on admission. Only 10% of patients required a change in antidiabetic treatment with insulin therapy at discharge. In our study, 89% of all patients did not require short-term home oxygen therapy at discharge. CONCLUSIONS: Antidiabetic therapy taken before hospital admission did not protect patients against cytokine storm in COVID-19, but is very important in the pathophysiological stage of comorbidities. Paraclinical parameters at hospitalization showed differences in correlation with oral antidiabetic treatment like metformin or insulin therapy. Changing the antidiabetic treatment for a small percentage of patients in the group who had not been receiving insulin therapy before discharge was necessary. It is necessary for future studies to see all changes involved in antidiabetic treatment in patients with diabetes type 2 and obesity after SARS-CoV2 viral infection and its long-term evolution.

The Management of Obstructive Sleep Apnea Patients during the COVID-19 Pandemic as a Public Health Problem-Interactions with Sleep Efficacy and Mental Health.

With the onset of the COVID-19 outbreak, it was stipulated that patients with obstructive sleep apnea (OSA) may have a greater risk of morbidity and mortality and may even experience changes in their mental health. The aim of the current study is to evaluate how patients managed their disease (sleep apnea) during the COVID-19 pandemic, to determine if continuous positive airway pressure (CPAP) usage changed after the beginning of the pandemic, to compare the stress level with the baseline, and to observe if any modifications are related to their individual characteristics. The present studies highlight the level of anxiety, which was high among patients with OSA during the COVID-19 pandemic (p < 0.05), with its influence on weight control (62.5% of patients with high levels of stress gained weight) and sleep schedule (82.6% reported a change in sleep schedule). Patients with severe OSA and high levels of stress increased their CPAP usage (354.5 min/night vs. 399.5 min/night during the pandemic, p < 0.05). To conclude, in OSA patients, the presence of the pandemic led to a greater level of anxiety, changes in sleep schedule and weight gain because of job loss, isolation, and emotional changes, influencing mental health. A possible solution, telemedicine, could become a cornerstone in the management of these patients.

Histopathological Lung Findings in COVID-19 B.1.617.2 SARS-CoV-2 Delta Variant.

BACKGROUND: The Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant. METHODS: The study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody). RESULTS: Virology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells. CONCLUSIONS: The histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.

Asymptomatic Esophageal Necrosis in a Patient with Recent COVID-19: The First Case Diagnosed through Autopsy.

Acute esophageal necrosis is a rare condition, characterized by a distinctive endoscopic/necropsic image-circumferential black area of the esophagus. This paper presents a case of a 78-year-old patient with recent history of a severe form of COVID-19 (2 months previously), with multiple comorbidities, which presents sudden death in hospital. Anatomic-pathological autopsy showed extensive esophageal necrosis, pulmonary thromboses, and coronarian and aortic atherosclerosis. The histopathological examination revealed necrosis of the esophageal mucosa and phlegmonous inflammation extended to the mediastinum, chronic pneumonia with pulmonary fibrosis, viral myocarditis, papillary muscle necrosis, and pericoronary neuritis. Thromboses and necroses were identified also in the liver, pancreas, and adrenal glands. Post-COVID-19 thromboses can manifest late, affecting various vascular territories, including esophageal ones. Their clinical picture may be diminished or absent in elderly and/or diabetic patients.

Obesity Impact on SARS-CoV-2 Infection: Pros and Cons "Obesity Paradox"-A Systematic Review.

BACKGROUND: During the last years, the COVID-19 pandemic meets the pandemic generated by obesity, raising many questions regarding the outcomes of those with severe forms of infection. METHODS: The present systematic review summarises and analyses the data providing evidence for or against the "obesity-paradox" in COVID-19 patients. After applying the inclusion and exclusion criteria, 23 studies were included. We also analysed the presumably underlying basic mechanisms. RESULTS: The patients with a body mass index (BMI) of 30-40 kg/m2 presented severe symptoms that led to intensive care unit (ICU) admission but not increased death rate. Those with a higher degree of obesity, with a BMI higher than 40 kg/m2, led to a rise in the death rate, particularly in young patients. Obesity was associated with a higher rate of ICU admission but was not determined as an independent predictor of increased mortality. In contrast, some studies suggest a strong association between obesity or morbid obesity and the risk of death. CONCLUSIONS: The existence of "obesity-paradox" cannot be stated; our study presents obesity as a critical risk factor in the evolution of COVID-19.

Quantitative MRI of Pancreatic Cystic Lesions: A New Diagnostic Approach.

The commonly used magnetic resonance (MRI) criteria can be insufficient for discriminating mucinous from non-mucinous pancreatic cystic lesions (PCLs). The histological differences between PCLs' fluid composition may be reflected in MRI images, but cannot be assessed by visual evaluation alone. We investigate whether additional MRI quantitative parameters such as signal intensity measurements (SIMs) and radiomics texture analysis (TA) can aid the differentiation between mucinous and non-mucinous PCLs. Fifty-nine PCLs (mucinous, n = 24; non-mucinous, n = 35) are retrospectively included. The SIMs were performed by two radiologists on T2 and diffusion-weighted images (T2WI and DWI) and apparent diffusion coefficient (ADC) maps. A total of 550 radiomic features were extracted from the T2WI and ADC maps of every lesion. The SIMs and TA features were compared between entities using univariate, receiver-operating, and multivariate analysis. The SIM analysis showed no statistically significant differences between the two groups (p = 0.69, 0.21-0.43, and 0.98 for T2, DWI, and ADC, respectively). Mucinous and non-mucinous PLCs were successfully discriminated by both T2-based (83.2-100% sensitivity and 69.3-96.2% specificity) and ADC-based (40-85% sensitivity and 60-96.67% specificity) radiomic features. SIMs cannot reliably discriminate between PCLs. Radiomics have the potential to augment the common MRI diagnosis of PLCs by providing quantitative and reproducible imaging features, but validation is required by further studies.

Glioblastoma Microenvironment and Cellular Interactions.

The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell-cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.

Multiple Faces of the Glioblastoma Microenvironment.

The tumor microenvironment is a highly dynamic accumulation of resident and infiltrating tumor cells, responsible for growth and invasion. The authors focused on the leading-edge concepts regarding the glioblastoma microenvironment. Due to the fact that the modern trend in the research and treatment of glioblastoma is represented by multiple approaches that target not only the primary tumor but also the neighboring tissue, the study of the microenvironment in the peritumoral tissue is an appealing direction for current and future therapies.

Ultrasonography in the Differentiation of Endometriomas from Hemorrhagic Ovarian Cysts: The Role of Texture Analysis.

The ultrasonographic (US) features of endometriomas and hemorrhagic ovarian cysts (HOCs) are often overlapping. With the emergence of new computer-aided diagnosis techniques, this is the first study to investigate whether texture analysis (TA) could improve the discrimination between the two lesions in comparison with classic US evaluation. Fifty-six ovarian cysts (endometriomas, 30; HOCs, 26) were retrospectively included. Four classic US features of endometriomas (low-level internal echoes, perceptible walls, no solid components, and less than five locules) and 275 texture parameters were assessed for every lesion, and the ability to identify endometriomas was evaluated through univariate, multivariate, and receiver operating characteristics analyses. The sensitivity (Se) and specificity (Sp) were calculated with 95% confidence intervals (CIs). The texture model, consisting of seven independent predictors (five variations of difference of variance, image contrast, and the 10th percentile; 100% Se and 100% Sp), was able to outperform the ultrasound model composed of three independent features (low-level internal echoes, perceptible walls, and less than five locules; 74.19% Se and 84.62% Sp) in the diagnosis of endometriomas. The TA showed statistically significant differences between the groups and high diagnostic value, but it remains unclear if the textures reflect the intrinsic histological characteristics of the two lesions.

Physalis alkekengi L. Extract Reduces the Oxidative Stress, Inflammation and Apoptosis in Endothelial Vascular Cells Exposed to Hyperglycemia.

To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.

A Phytocomplex Consisting of Tropaeolum majus L. and Salvia officinalis L. Extracts Alleviates the Inflammatory Response of Dermal Fibroblasts to Bacterial Lipopolysaccharides.

BACKGROUND: The antimicrobial activity and effects of a phytocomplex consisting of Tropaeolum flos (T) and Salviae folium (S) extracts on the cytokine levels and transcription factors on dermal fibroblast BJ exposed to bacterial lipopolysaccharides were examined. METHODS: In order to select the most optimal combination ratio of the two extracts for using in vitro, the physicochemical characterization of vegetal extract mixtures was performed and the antioxidant and antibacterial activities were evaluated on five different formulations of T : S, namely, 1 : 1, 1 : 2, 2 : 1, 3 : 1, and 1 : 3. The best combination of bioactive compounds with regard to antioxidant and antibacterial activities (T : S 1 : 2) was selected for in vitro evaluation of the anti-inflammatory effect. Human dermal fibroblast BJ cells were treated with two doses of the extract mixture and then exposed to bacterial lipopolysaccharides (LPS). The levels of the cytokines involved in inflammatory response, namely, interleukin- (IL-) 6, tumor necrosis factor- (TNF-) α, IL-31, and IL-33, were quantified by ELISA, and the expression of transcription factors, namely, signal transducer and activator of transcription (STAT) 3, nuclear factor kappa B (NFκB), and phosphorylated NFκB (pNFκB), were evaluated by western blot analysis. RESULTS: The results have shown that the mixture of T : S 1 : 2 exhibited significant antibacterial effects on Staphylococcus aureus ATCC 25923. LPS exposure increased the cytokine levels in BJ cells and enhanced the NFκB expression. The pretreatment of BF cells exposed to LPS with the two doses of the extract mixture markedly inhibited the increase of IL-33 and TNF-α levels and amplified the NFκB expression and its activation, especially with the high dose. The low doses of the extract reduced NFκB expression but increased its activation. CONCLUSIONS: These experimental findings suggest that the mixture of T : S 1 : 2 can exert some protection against bacterial infections and inflammation induced by LPS in BJ cells being a good therapeutic option in related conditions associated with inflammation.

Papilian's anatomy - celebrating six decades.

Victor Papilian was born an artist, during high school he studied music in order to become a violinist in two professional orchestras in Bucharest. Later on he enrolled in the school of medicine, being immediately attracted by anatomy. After graduating, with a briliant dissertation, he became a member of the faculty and continued to teach in his preferred field. His masters, Gh. Marinescu and Victor Babes, proposed him for the position of professor at the newly established Faculty of Medicine of Cluj. Here he reorganized the department radically, created an anatomy museum and edited the first dissection handbook and the first Romanian anatomy (descriptive and topographic) treatise, both books received with great appreciation. He received the Romanian Academy Prize. His knowledge and skills gained him a well deserved reputation and he created a prestigious school of anatomy. He published over 250 scientific papers in national and international journals, ranging from morphology to functional, pathological and anthropological topics. He founded the Society of Anthropology, with its own newsletter; he was elected as a member of the French Society of Anatomy. In parallel he had a rich artistic and cultural activity as writer and playwright: he was president of the Transylvanian Writers' Society, editor of a literary review, director of the Cluj theater and opera, leader of a book club and founder of a symphony orchestra.

A sculpture masterpiece for the teaching of anatomy.

BACKGROUND AND AIM: The study of anatomy remains the backbone of medical education in the first years. There is a constant need for educational materials that enable the assimilation of knowledge by students. The casts after human bodies have not lost the value, even in the era of virtual education. We present in this paper a museal item destined to improve the anatomy teaching. METHODS: Given the existence in the department of anatomy from Cluj -Napoca of an item of exceptional artistic and scientific value, we intensively searched Pubmed and Scopus, as well as by manual search of printed only documents, for all papers related to the muscle man by Brancusi created for educational purposes of anatomy students. RESULTS: This paper presents summary data from the biography of the creators of this item, the world famous sculptor Constantin Brancusi and the professor of anatomy and surgery from Bucharest Dimitrie Gerota. We also describe this item and the conditions which generated it. CONCLUSION: Teaching anatomy relies on the quality of the didactic support. The muscle man by Brancusi is a very realistic reproduction of a man, very useful for anatomical training and teaching.