Unraveling the Immune Microenvironment in Diffuse Large B-Cell Lymphoma: Prognostic and Potential Therapeutic Implications.

Diffuse large B cell lymphoma (DLBCL) is a multifaceted condition characterized by significant diversity in its molecular and pathological subtypes and clinical manifestation. Despite the progress made in the treatment of DLBCL through the development of novel drugs, an estimated one-third of patients encounter relapse or acquire refractory disease. The tumor microenvironment (TME) of DLBCL, a complex network consisting of cellular and noncellular components that engage in interactions with the tumor, is a parameter that is gaining increasing attention. The TME comprises both the immune and nonimmune microenvironments. The immune microenvironment comprises natural killer (NK) cells, dendritic cells (DCs), tumor-associated macrophages (TAMs), neutrophils, myeloid-derived suppressor cells (MDSCs), and T and B lymphocytes. The nonimmune microenvironment consists of the extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), mesenchymal stromal cells, and other molecules that are secreted. Despite ongoing research, the exact impact of these components and their interaction on the progression of the disease remains elusive. A comprehensive review of significant discoveries concerning the cellular and noncellular constituents, molecular characteristics, and treatment response and prognosis of the TME in DLBCL, as well as the potential targeting of the TME with novel therapeutic approaches, is provided in this article.

The right lymphatic duct: basic anatomy and clinical relevance.

The anatomical variability of the thoracic duct and the right lymphatic duct predisposes them to inadvertent damage following head and neck surgery thereby leading to chyle leak which is an uncommon complication with potentially significant associated morbidity. Although chyle leak is predominately associated with left-sided neck surgery, it also occurs as a complication of the right-sided neck dissection. Variable figures concerning chyle leakage after right-sided neck dissections were reported, ranging from 0 per cent to higher prevalences such as 14%, 24%, 33% and 60% of total cases of chyle leakages associated with neck surgery. The right-sided complications may implicate the right lymphatic duct and right-sided terminations of the thoracic duct into the venous system which occur in about 1-6% of humans. Other clinically relevant conditions involving the right-sided major lymphatic vessels include chyle leaks following right anterior cervical spine surgery, cysts of the right lymphatic duct and dilatation of the right lymphatic duct in the setting of recurrent cervical swelling. This article presents a review of the literature concerning the basic anatomy and the clinical relevance of the right lymphatic duct and the right-sided terminations of the thoracic duct into the venous circulation.

Anatomical variations of the great saphenous vein at the saphenofemoral junction. A cadaveric study and narrative review of the literature.

OBJECTIVES: The great saphenous vein is the lower limb's longest and thickest-walled superficial vein. Its anatomy is complex, while its anatomical variations are widespread. This study aimed to illustrate the anatomy and variations of the great saphenous vein at the saphenofemoral junction. METHODS: The study was conducted on 75 fresh-frozen cadaveric lower limbs. Cadavers with evidence of prior leg surgery or trauma and any congenital abnormality or gross deformity were excluded. The saphenofemoral junction was studied in detail with emphasis on the number, incidence, draining pattern of tributaries, and duplication of the great saphenous vein. RESULTS: Out of the 75 cadaveric lower limbs, 57.3% were obtained from males, and 42.7% were obtained from females. The mean age of the cadaveric lower extremities was 66.6 years (range 42-91). The number of tributaries at the saphenofemoral junction varied from 0 to 7, with a mean of 3.8. The most frequent number of branches was 4-5 in 61.3% of cases. The most consistent tributary was the superficial external pudendal vein, while the posterior accessory great saphenous vein was the least frequent tributary. 80% of the branches drained into the saphenofemoral junction directly (53.3%) or by a common trunk (26.7%%). The most frequent common trunk was the superficial epigastric and superficial circumflex iliac vein (10.7%). The rest 20% of the tributaries drained directly into the common femoral vein. The commonest branch reaching the common femoral vein was the superficial external pudendal vein (10.7%). Duplication of the great saphenous vein was observed in 2.7% of the cases. CONCLUSIONS: There is a significant variation of tributaries at the saphenofemoral junction regarding the number, incidence, draining pattern of branches, and duplication of the great saphenous vein.

Prevalence and risk factors of phlebosclerosis in the great saphenous vein.

OBJECTIVES: Phlebosclerosis is a fibrous degeneration of the vein wall, predominantly the intima, with or without calcification. The prevalence and etiology of phlebosclerosis of the great saphenous vein are not well documented. This study aimed to estimate the prevalence and define the risk factors of phlebosclerosis of the great saphenous vein. METHODS: The study was conducted on 300 volunteers who underwent duplex ultrasound. Volunteers with symptoms and signs of acute or chronic venous disease or known varicose veins, thrombosis, chronic vein insufficiency, and any operation in the lower extremities were excluded. The imaging hallmarks of phlebosclerosis include wall brightness, calcification, and increased wall thickness. Demographics of the volunteers (sex, age, weight, and height), Body Mass Index (BMI) and the presence of smoking, hypertension, diabetes mellitus, and dyslipidemia were recorded. Data obtained were consolidated and statistically evaluated using SPSS Version 16. RESULTS: Of the 300 volunteers who underwent duplex ultrasound, 60.3% were females, and 39.7% were males. The mean age was 60 ± 13, while the mean BMI was 26.01 ± 4.76. Moreover, 66.3% were non-smokers, and 62.3%, 81.3%, and 58.7% did not suffer from hypertension, diabetes mellitus, and dyslipidemia, respectively. The prevalence of phlebosclerosis was found to be 2.3%. Hypertension was a risk factor for the development of phlebosclerosis (p = 0.045). Moreover, there was a link between phlebosclerosis and age, as volunteers with phlebosclerosis were older than volunteers without phlebosclerosis (74.2 vs 59.11 years, p < 0.001). CONCLUSIONS: The prevalence of phlebosclerosis of the great saphenous vein is low, specifically 2.3%. Hypertension and increased age are risk factors for the development of phlebosclerosis. Both sexes are equally affected, while BMI, smoking, diabetes mellitus, and dyslipidemia do not contribute to the development of phlebosclerosis.

Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets.

Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets, along with their protein composition, mainly including perilipins, have been implicated in the etiology of the disease. These proteins have garnered increasing attention as a pivotal regulator since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications on the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis, chaperone-mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.

Cytokines in Immune-mediated "Non-infectious" Uveitis.

Uveitis is a significant cause of ocular morbidity and accounts for approximately 5 - 10% of visual impairments worldwide, particularly among the working-age population. Infections are the cause of ~ 50% cases of uveitis, but it has been suggested that infection might also be implicated in the pathogenesis of immune-mediated "non-infectious" uveitis. There is growing evidence that cytokines (i.e., interleukins, interferons, etc.) are key mediators of immune-mediated "non-infectious" uveitis. For example, activation of the interleukin-23/interleukin-17 signalling pathway is involved in immune-mediated "non-infectious" uveitis. Studies in animal models have been important in investigating the role of cytokines in uveitis. Recent studies of clinical samples from patients with uveitis have allowed the measurement of a considerable array of cytokines even from very small sample volumes (e.g., aqueous and vitreous humour). The identification of complex patterns of cytokines may contribute to a better understanding of their potential pathogenetic role in uveitis as well as to an improved diagnostic and therapeutic approach to treat these potentially blinding pathologies. This review provides further insights into the putative pathobiological role of cytokines in immune-mediated "non-infectious" uveitis.

Chronic Inflammatory Demyelinating Polyneuropathy and Evaluation of the Visual Evoked Potentials: A Review of the Literature.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder characterised by the progressive demyelination of peripheral nerves, resulting in motor and sensory deficits. While much research has focused on clinical and electrophysiological aspects of CIDP, there is an emerging interest in exploring its impact on the visual system through visual evoked potentials (VEPs). This comprehensive review synthesises existing literature on VEP findings in CIDP patients, shedding light on their potential diagnostic and prognostic value. The review thoroughly examines studies spanning the last two decades, exploring VEP abnormalities in CIDP patients. Notably, VEP studies have consistently revealed prolonged latencies and reduced amplitudes in CIDP patients compared to healthy controls. These alterations in VEP parameters suggest that the demyelinating process extends beyond the peripheral nervous system to affect the central nervous system, particularly the optic nerve and its connections. The correlation between VEP abnormalities and clinical manifestations of CIDP, such as visual impairment and sensory deficits, underscores the clinical relevance of VEP assessment in CIDP management. Furthermore, this review addresses the potential utility of VEPs in aiding CIDP diagnosis and monitoring disease progression. VEP abnormalities may serve as valuable biomarkers for disease activity, helping clinicians make timely therapeutic decisions. Moreover, this review discusses the limitations and challenges associated with VEP assessment in CIDP, including variability in recording techniques and the need for standardised protocols. In conclusion, this review highlights the evolving role of VEPs as a non-invasive tool in CIDP evaluation. The consistent VEP abnormalities observed in CIDP patients suggest the involvement of the central nervous system in this demyelinating disorder. As our understanding of CIDP and its pathophysiology continues to evolve, further research in this area may lead to improved diagnostic accuracy and monitoring strategies, ultimately enhancing the clinical management of CIDP patients.

Ocular toxoplasmosis: a review of the current diagnostic and therapeutic approaches.

PURPOSE: This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up and therapeutic approach of ocular toxoplasmosis focusing mainly on the postnatally acquired form of the disease. METHODS: A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. RESULTS: Ocular toxoplasmosis is one of the most frequent infectious etiologies of posterior uveitis. It typically presents with retinochoroiditis. Setting an accurate diagnosis depends to a considerable degree on detecting characteristic clinical characteristics. In addition to the evaluation of clinical features, the diagnosis of toxoplasmosis relies at a large degree on serologic testing. The detection of the parasite DNA in the aqueous or vitreous humor can provide evidence for a definitive diagnosis. The current mainstay for the treatment, if necessary, is the use of oral antibiotic with systemic corticosteroids. Recent evidence suggests other therapeutic approaches, such as intravitreal antibiotics can be used. CONCLUSION: Recent developments in the diagnostic and therapeutic approach have contributed to preventing or limiting vision loss of patients suffering from ocular toxoplasmosis. Further studies are required to provide a better understanding of epidemiology, pathogenesis, diagnosis, and treatment with a significant impact on the management of this challenging clinical entity.

Concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma in a patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma.

The phenomenon of histiocytic/dendritic cell sarcomas arising through transformation of a pre-existed lymphoproliferative disease is called transdifferentiation. Langerhans cell sarcoma transdifferentiating from chronic lymphocytic leukemia/small lymphocytic lymphoma is extremely rare and all the reported cases were localized in lymph nodes. We present a case of concurrent cutaneous localization of Langerhans cell sarcoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, in which the chronic lymphocytic leukemia/small lymphocytic lymphoma preceded the development of the Langerhans cell sarcoma. A cutaneous lesion from a 63-year-old patient with a history of chronic lymphocytic leukemia/small lymphocytic lymphoma was biopsied. The histologic examination revealed a mixture of two cell populations infiltrating diffusely the dermis. The first was composed of small lymphoid cells with somewhat monotonous appearance and mild nuclear atypia positive for PAX5, CD79a, CD20, CD23, CD5, and LEF1. The second was composed of large cells with abundant cytoplasm and pleomorphic nuclei. These cells were positive for CD1a, CD207, and S100 protein and exhibited a high mitotic rate and a high MIB-1 immunostaining index. Therefore, two different entities, chronic lymphocytic leukemia/small lymphocytic lymphoma and Langerhans cell sarcoma, were detected in the same skin fragment. The patient died 3 years after initial diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma.

Phlebosclerosis in lower extremities veins - a systematic review.

Phlebosclerosis is a venous wall degenerative disease which has gained little popularity in the literature due to its uncertain clinical significance. The objective of this review is to evaluate the epidemiology, etiology and clinical significance of phlebosclerosis in lower extremities veins, particularly the effect of preexisting phlebosclerosis of the great saphenous vein on vein graft patency. Medline was searched from inception until November 1, 2019. Reference lists of included studies were scanned. Only articles published after 1949 were included. Two reviewers independently screened titles/abstracts and full-text papers for any study design in relation to phlebosclerosis in lower extremities veins and abstracted data. A total of 16 Cohort studies and one case-control study (3708 participants, mean age 61.8 years, 59.3 % men, and 40.7 % women) were included after screening 317 titles and abstracts, and 80 full-text articles. The incidence of phlebosclerosis ranged from 1.5-9.7 % depending on the radiological features. On the contrary, the incidence of the phlebosclerotic great saphenous vein prior to its use as a vein graft was 26.9-91 % on histological examination. The small saphenous vein was the most common location of phlebosclerosis followed by the great saphenous vein. There is a link between phlebosclerosis and age, venous insufficiency and haemodialysis. As for the vein graft patency seven studies demonstrated a correlation between preexisting phlebosclerosis and vein graft stenosis, whereas three studies failed to prove any association. In conclusion, the radiological incidence of phlebosclerosis depended on the ultrasound findings. Its presence in the great saphenous vein prior to its use as a vein graft is established on histological examination. The small saphenous vein is mainly affected. Risk factors included age, haemodialysis, and venous insufficiency. Preexisting wall thickness of the great saphenous vein graft seemed to affect negatively its patency in bypass surgery.

Antigen-presenting cells in ocular surface diseases.

PURPOSE: To review the role of antigen-presenting cells (APC) in the pathogenesis of ocular surface diseases (OSD). METHODS: A thorough literature search was performed in PubMed database. An additional search was made in Google Scholar to complete the collected items. RESULTS: APCs have the ability to initiate and direct immune responses and are found in most lymphoid and non-lymphoid tissues. APCs continuously sample their environment, present antigens to T cells and co-ordinate immune tolerance and responses. Many different types of APCs have been described and there is growing evidence that these cells are involved in the pathogenesis of OSD. OSD is a complex term for a myriad of disorders that are often characterized by ocular surface inflammation, tear film instability and impairment of vision. CONCLUSIONS: This review summarizes the current knowledge concerning the immunotopographical distribution of APCs in the normal ocular surface. APCs appear to play a critical role in the pathology of a number of conditions associated with OSD including infectious keratitis, ocular allergy, dry eye disease and pterygium.

Safe zones in volar portals for wrist arthroscopy, evaluation of central portal : a cadaveric study.

The purpose of this cadaveric study is to determine safe zones utilizing volar portals for wrist arthroscopy, by quantitatively describing the neurovascular relationships of a volar radial and a volar ulnar wrist arthroscopy portals in comparison with those of a newly described volar central portal (7) , considering the advantages in visualization of volar portals for wrist arthroscopy over the standard dorsal (19) . The neurovascular structures and the tendons of nine frozen human cadaveric upper limbs were exposed, while the aforementioned volar portal sites were pointed out with pins. The horizontal distance between the portals and the closest neurovascular branch or tendon was measured with a digital caliper, followed by statistical analysis of the data. The median interquartile range distances from portals to structures at risk were measured and safe zones around each portal were established. This study provides a safe approach to the volar radial and ulnar aspects of the radiocarpal and midcarpal joints, while volar radial and ulnar portals should be considered for inclusion in the arthroscopic examination of any patient with radial and ulnar sided wrist pain respectively (17,18) . Regarding the volar central portal, it is reproducible, safe and both the above joints can be inspected through one single incision (7) .

Association between the capitate-triquetrum distance and carpal collapse in static scapholunate instability.

Long-standing scapholunate instability frequently leads to progressive deterioration of the adjacent joint cartilages in a consistent repetitive sequence of arthritis. The purpose of this study was to investigate whether the capitate-triquetrum distance is related with the occurrence of carpal collapse in cases of static scapholunate instability. In this retrospective study, 41 patients formed two groups based on the capitate-triquetrum distance; twenty-four with distance of less than 5mm and 17 with distance of 5mm or more. No significant difference was detected with respect to age, sex distribution, dominant hand involvement, initial treatment and time from injury to final x-rays. Three patients (3/24, 12.5%) of the C-T < 5mm group and 10 patients (10/17, 58.8%) of the C-T ≥ 5mm group had no sign of carpal collapse. This difference was statistically significant (p=0.017). Capitate-triquetrum distance could reliably contribute in the decision making process in difficult cases of static scapholunate instability.

The contribution of the medial retinaculum as a restraining factor to the patella dislocation.

The objective of this study was to evaluate the contribution of the medial retinaculum to the stability of the patella, for several angles of knee flexion. For six cadaveric knees, the patella and patella retinaculum were exposed, and the force required to dislocate the patella laterally by 5 mm was measured, in 0, 45 and 90 degrees of knee flexion, preserving and dissecting the medial retinaculum. Wilcoxon singed rank test (SPSS, version 23, Chicago, USA) was used for data analysis. A p value of < 0.05 was considered as statistically significant. The force required to displace the patella laterally is smaller with the medial retinaculum dissected than intact, in 0, 45 and 90 degrees (p = 0.028, p = 0.046, p = 0.027 respectively). The lateral displacement force is greater as the flexion angle increases, with medial retinaculum intact or dissected (p = 0.028). Thus, an intact medial retinaculum provides more stability against lateral displacement forces to the patella, especially in lower flexion angles. Consequently, surgical methods reinforcing the medial retinaculum combined or not with lateral retinaculum release, are of great importance in the plan of the orthopedic surgeons. The engagement of the bones during flexion of the knee contributes significantly to the stability of the patella.

Correlation between Manchester Grading Scale and American Orthopaedic Foot and Ankle Society Score in Patients with Hallux Valgus.

OBJECTIVE: To evaluate the correlation between the Manchester Grading Scale and the American Orthopaedic Foot and Ankle Society (AOFAS) score in patients with a hallux valgus deformity. SUBJECTS AND METHODS: The study sample included 181 feet of 122 patients with hallux valgus and 424 feet of 212 individuals without hallux valgus deformity as the control group. The severity of hallux valgus, utilizing a relative nonmetric scale, the Manchester Grading Scale, and the metric AOFAS score, was determined for all individuals in the hallux valgus and control groups. SPSS version 18 (Chicago, Ill., USA) was used for data analysis. RESULTS: According to the Manchester Grading Scale, the 424 feet of the normal group were classified as 'no deformity'. In the hallux valgus group, 85 feet were classified as 'mild deformity', 67 as 'moderate deformity' and 29 as 'severe deformity'. The AOFAS total score in the control group was 99.14. In the hallux valgus group, patients with mild or moderate deformity had total scores of 86.20 and 68.19, respectively. For those with severe hallux valgus, the total score was 44.69 and the differences were statistically significant (p = 0.000). Using the Pearson correlation, strong negative correlations were found between the AOFAS score and the hallux valgus angle (HVA; r = -0.899, p = 0.000). Strong negative correlations were demonstrated between the AOFAS score and the first intermetatarsal angle (IMA) as well (r = -0.748, p = 0.000). CONCLUSIONS: The AOFAS score was negatively associated with the Manchester Grading Scale, HVA and first IMA. As the severity of hallux valgus increased, the AOFAS score seemed to decrease.

Association between the capitate-triquetrum distance and carpal collapse in scaphoid nonunion.

The effect of the lunate type on carpal collapse in cases of scaphoid nonunion has not been thoroughly investigated. The purpose of the present study was to determine whether any association exists or not between the capitate-triquetrum distance and occurrence of carpal collapse in cases of scaphoid nonunion. In a retrospective study, 76 patients with scaphoid nonunion formed two groups based on the capitate-triquetrum distance: forty-three patients with distance of less than 5 mm and 33 patients with distance of 5 mm or more. The two groups were comparable with respect to sex distribution, age, dominant hand involvement, manual labor, nonunion location and time from injury to final x-rays. Six patients (13.9%) in the capitate-triquetrum<5 mm group and 13 patients (39.4%) in the capitate-triquetrum≥5 mm group had no signs of collapse, with significant difference (p<0.05). Capitate-triquetrum distance could contribute in the decision making process for cases of scaphoid nonunion without straightforward indication for surgical intervention.

Expression Patterns of GATA3 in Classical Hodgkin Lymphoma: A Clinico-Pathological Study.

GATA3 is a transcription factor involved in T-cell maturation and has been previously shown to be aberrantly overexpressed in malignant Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL). However, the immunophenotypes of the cell types expressing GATA3 have not been precisely characterized so far in cHL tissues. In this single-center retrospective cohort study we analyzed the expression patterns of GATA3 alone and in combination with B, T, NK or macrophage-associated markers in 73 cases with newly diagnosed cHL and investigated for a possible correlation with clinical and laboratory parameters. Immunohistochemistry (single and double) was performed using GATA3 alone and in combination with CD20, CD3, CD56, CD68, CD30 or CD15. Clinical and laboratory parameters were collected and correlated with the expression of GATA 3. GATA3 nuclear expression was found in HRS cells in 39/73 (54%) cases of cHL. The Nodular Sclerosis (NS) subtype showed the highest positivity rate (35/56, 63%), followed by mixed cellularity (MC; 4/14, 29%) and lymphocyte rich (LR; 0/3). Double immunostainings showed that GATA3 was expressed by CD30+ or CD15+ HRS cells and a few CD3+ T-cells, whereas GATA3 expression was not detected in CD20, CD56 or CD68+ cells. GATA3-negative cHL was significantly associated with unfavorable prognostic factors such as older age at diagnosis and increased levels of serum ß2-microglobulin. The heterogenous expression patterns of GATA3 in HRS cells that were observed in a substantial proportion of cHL, mainly in the NS subtype, further support the biological heterogeneity of cHL.

Anatomy of the lymphatics in normal stomach and gastric carcinomas.

The lymphatic system is composed of lymphoid organs/tissues and a complex network of lymphatic vessels that transport interstitial fluid, antigens, lipids, immune cells, and other materials in the body. There is growing evidence that lymphatic vasculature is associated with many pathological conditions such as lymphedema and cancer progression and metastasis. Thus, improved understanding of the anatomical features, the molecular profile and the function of the lymphatic vasculature may provide innovative approaches for disease prevention and treatment. This article aims to present a comprehensive review of the gastric lymphatic anatomy and its importance in the pathology, treatment and prognosis of gastric carcinomas.

Cytokine effects on cell survival and death of A549 lung carcinoma cells.

PURPOSE: IL-13, TNF-α and IL-1ß have various effects on lung cancer growth and death, but the signaling pathways mediating these effects have not been extensively analyzed. Therefore, the effects of IL-13, TNF-α and IL-1ß alone, and in combination with Fas, on cell viability and death as well as major signaling pathways involved in these effects were investigated in A549 lung carcinoma cells. RESULTS: Using MTT and flow cytometry, IL-13, TNF-α and IL-1ß pretreatment decreased Fas-induced cell death. These anti-cell death effects were attenuated by pretreatment with inhibitors of Nuclear factor-κB [NF-κB], Phoshatidylinositole-3 kinase [PI3-K], JNK, p38 and ERK1/2 pathways. Using Western blot, IL-13, TNF-α and IL-1ß treated cells showed time-dependent expression of p-ERK1/2, p-p38, p-JNK, p-Akt and p-IκBα proteins, decreased IκBα protein expression, no cleavage of Caspase-3 and PARP1 proteins and no notable alterations of Fas protein. IL-13 and TNF-α treated cells showed time-dependent increase of FLIPL expression. CONCLUSION: IL-13, TNF-α and IL-1ß attenuate the pro-cell death effects of Fas on A549 cells, at least partially, by pathways involving the NF-κB, PI3-K and MAP kinases, but not by alterations of Fas protein expression. The IL-13 and TNF-α cell survival effects may also be due to increased expression of FLIPL protein.

Oxidative Stress-Induced Cellular Senescence: Is Labile Iron the Connecting Link?

Cellular senescence, a cell state characterized by a generally irreversible cell cycle arrest, is implicated in various physiological processes and a wide range of age-related pathologies. Oxidative stress, a condition caused by an imbalance between the production and the elimination of reactive oxygen species (ROS) in cells and tissues, is a common driver of cellular senescence. ROS encompass free radicals and other molecules formed as byproducts of oxygen metabolism, which exhibit varying chemical reactivity. A prerequisite for the generation of strong oxidizing ROS that can damage macromolecules and impair cellular function is the availability of labile (redox-active) iron, which catalyzes the formation of highly reactive free radicals. Targeting labile iron has been proven an effective strategy to counteract the adverse effects of ROS, but evidence concerning cellular senescence is sparse. In the present review article, we discuss aspects of oxidative stress-induced cellular senescence, with special attention to the potential implication of labile iron.