Objectives: Nuclear factor κB (NF-κB) is a superfamily of transcription factors that plays a key role in cancer genesis and progression. The present study aimed to examine the expression of NF-κB/p65 in breast cancer and its relationship with prognostic markers such as tumour grade, tumour size, hormone receptors, and HER-2. Methods: Ninety-nine unselected formalin-fixed paraffin-embedded invasive ductal and lobular tissue sections were evaluated by immunohistochemistry methods to measure the expression of NF-κB/p65, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and Ki-67. We assessed the correlation between NF-κB/p65 and clinicopathological parameters. Results: NF-κB/p65 was found only in the cytoplasm and positively correlated with large tumours (≥2 cm) and high-grade tumours (p < 0.001 and p = 0.018, respectively). Other breast cancer markers, such as histological type (p = 0.766), HER-2 (p = 0.416), PR (p = 0.356), and ER (p = 0.606), had no significant link with the expression of NF-κB/p65. Furthermore, no significant relation with the Ki-67 marker was detected (p = 0.117). Conclusions: The current study is indicative of a link between overexpression of NF-κB/p65 and both large tumour size and higher grade. This suggests that the expression of NF-κB/p65 is associated with aggressive biological activity in breast cancer; elucidating the mechanisms that lead to NF-κB/p65 cytoplasmic accumulation could lead to the development of novel therapeutic methods.

Obesity has reached global epidemic proportions and it affects the development of insulin resistance, type 2 diabetes, fatty liver disease and other metabolic diseases. Membrane lipids are important structural and signaling components of the cell membrane. Recent studies highlight their importance in lipid homeostasis and are implicated in the pathogenesis of fatty liver disease. Here, we discuss the numerous membrane lipid species and their metabolites including, phospholipids, sphingolipids and cholesterol, and how dysregulation of their composition and physiology contribute to the development of fatty liver disease. The development of new genetic and pharmacological mouse models has shed light on the role of lipid species on various mechanisms/pathways; these lipids impact many aspects of the pathophysiology of fatty liver disease and could potentially be targeted for the treatment of fatty liver disease.

Doxorubicin (Dox) has limited efficiency in breast cancer (BC) due to drug-acquired resistance. The epithelial–mesenchymal transition (EMT) plays a major role in the survival and drug resistance of cancer cells. It was suggested that the JNK pathway was implicated in the response to Dox by regulating EMT. DUSP4/or MKP-2 is a well-known regulator of the JNK pathway and was found to be highly expressed in BC. However, its functional significance is not yet fully understood. In the present study, the possible involvement of MKP-2 in Dox-induced EMT was investigated in breast cancer cells. Immunohistochemistry for tissues obtained from BC patients (n = 108) revealed 71.3% of tissues stained positively for MKP-2 while only 28.7% stained negatively. However, MKP-2 protein expression exhibited no significant relationship between BC prognostic factors, such as histological grade, histological type, hormonal status, and Ki-67 marker, its expression was significantly correlated with age 40 or below. In MDA-MB-231 cells, Dox-induced phosphorylation of JNK was sufficiently enhanced in MKP-2 silenced cells. This resulted in the attenuation of Dox-induced EMT, cell cycle arrest, and ultimately accelerated apoptosis. It was confirmed that the acquisition of Dox sensitivity by MKP-2 silencing largely depends on the stimulation of the JNK pathway. Indeed, results showed that overexpressing MKP-2 in non-tumorigenic MCF-12A cells dramatically inhibited Dox-induced JNK activation and, subsequently, cell death. The present study, to our knowledge, is the first to provide evidence for the potential role of MKP-2 in chemoresistance to Dox through modulating the JNK pathway and enhancing EMT.

Background: Camel urine (CU) has been used as traditional treatment in the Arabian Peninsula for centuries. Although, researchers have reported CU anti-cancer effects, the exact mechanism(s) of action involved has not been fully elucidated. The epithelial–mesenchymal transition EMT is a phenotypic switch that promotes the acquisition of a fibroblastoid-like morphology by epithelial tumor cells, resulting in enhanced tumor cell motility and invasiveness. EMT has been shown to contribute to metastasis and chemoresistance of carcinomas. For that, in the present study, we have assessed the potential mechanism (s) by which CU exert its anti-cancer effects and its possible synergistic therapeutic effect with Doxorubicin (DOX) in breast cancer cells. Methods: Determination of anti-proliferative and apoptosis validation of CU was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT), annexin-V-fluorescein isothiocyanate assays, and Western blot. EMT protein markers, migration and invasion of cells were determined by Western blot or immunofluorescent staining, Scratch assay, Transwell invasion assay, respectively. Results: CU applied a significant anti-cancer effect on breast cancer cells via induction of DNA damage and apoptosis in a concentration- and time-dependent manner. Also, CU remarkably reversed the EMT by downregulating N-cadherin and Vimentin expression and upregulating E-cadherin expression. As a result, the stemness, migration and invasion of breast cancer cells were also inhibited, which was likely mediated by NF-κB-Snail signalling pathway and its downstream inflammatory effectors. CU successfully enhanced DOX cytotoxicity by reversing EMT which possibly through inhibition of NF-κB-Snail signalling and subsequently inflammation. Thus, our study provides new mechanistic bases for the therapeutic application of CU that may improve the outcomes of anti-cancer chemotherapy.

Marine viruses are important components of microbial communities and influence their structure and dynamics, yet their variability remains poorly documented in the northwestern Arabian Gulf. Virus-like particle (VLP) abundance was monitored over four years at three coastal sites representing different environmental settings in Kuwait. Surface and depth samples were collected during each sampling period, along with physicochemical and nutrient data. VLP abundance fluctuated throughout the study and differed among sites and between depths. VLP counts tended to be higher at the southern site and near the surface, while the lowest values were recorded in Kuwait Bay. The three sites had distinct environmental characteristics, but relationships between VLP abundance and individual physicochemical variables varied among sites and seasons. When environmental, spatial, and temporal variables were considered together, Random Forest identified season, dissolved oxygen, and nutrients, particularly nitrate, among the important predictors of VLP abundance. Dissolved oxygen showed a nonlinear association with VLP abundance in the generalized additive model (GAM), and lower abundance at depth remained significant after accounting for the measured environmental variables, while site effects were not significant in this model. Overall, VLP abundance showed marked spatial and temporal variability across Kuwait coastal waters, with patterns associated with multiple environmental and seasonal factors. This four-year record provides a baseline for viral abundance in the northwestern Arabian Gulf and supports further investigation of the biological and environmental processes influencing viral dynamics in this highly variable coastal system.

Clinical outcomes of critically ill COVID-19 patients admitted to intensive care units (ICUs) remain heterogeneous, and factors influencing mortality require further characterization. This retrospective study evaluated clinical outcomes among 1,344 adult patients with confirmed COVID-19 admitted to ICUs across four governmental hospitals in Kuwait between June 2020 and December 2022. Survival outcomes were assessed using Kaplan–Meier survival analysis and compared by demographic and clinical characteristics. Cox proportional hazards regression was applied to identify factors associated with mortality, while comorbidities and treatment patterns were evaluated in relation to patient outcomes. Survival probability declined from 98% at 5 days to 50% at one year. Kaplan–Meier analysis showed significant differences in survival according to age and diabetes status. Non-survivors were older (66 vs. 55 years, p < 0.001), had a higher prevalence of diabetes (60.9%) and hypertension (70.4%), and experienced longer hospital stays. Hypoxia was strongly associated with mortality (p < 0.001). In Cox regression analysis, adjusted for pandemic admission wave to account for evolving ICU management, increasing age (HR = 1.04 per year, 95% CI 1.03–1.04), fever (HR = 1.18, 95% CI 1.01–1.39), and chronic kidney disease (HR = 1.40, 95% CI 1.11–1.76) were associated with higher mortality. In contrast, anti-inflammatory drug use was associated with reduced risk (HR = 0.52, 95% CI 0.43–0.63) as was anticoagulant (HR = 0.80, 95% CI 0.66–0.97). Antifungal use was associated with increased mortality risk (HR = 1.68, 95% CI: 1.30–2.16); however, associations involving medications likely reflect underlying disease severity and treatment indication rather than direct causal effects. Sensitivity analysis using a split follow-up at day 30 demonstrated that antifungal-associated risk was concentrated during the late follow-up period (HR = 2.10, days 31–365), consistent with late-onset secondary fungal infections among patients with prolonged critical illness.