Hanan Hassan Fouad

BACKGROUND: Melatonin, the controlling hormone of the sleep-wake cycle, has acquired attention due to its role in immunomodulation, anti-inflammation, as well as its proapoptotic effects. Wnt/β-catenin signaling can modulate cancer progression by promoting cell division and migration, while miR-let-7b may inhibit cell growth, migration, and invasion by affecting the function of adaptive immune cells. This work was designed to detect the effect of using melatonin as an immunomodulating therapeutic approach to control the progression of chemically induced hepatocellular carcinoma (HCC).

METHODS: Thirty male rats were equally divided into control, HCC, and melatonin-HCC groups. Animals in the HCC and melatonin-HCC groups were injected with diethylnitrosamine (intraperitoneal single dose) followed by repeated carbon-tetrachloride subcutaneous injection once weekly for six weeks. Melatonin was given from the first week of the study and continued during the process of HCC induction.

RESULTS: In the HCC group, the levels of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and Wnt/β-catenin expression significantly increased, while there was a downregulation of microRNA Let7b. Melatonin administration reversed these changes, along with an increase in hepatic content of interleukin-2 (IL-2) and caspase-3.

CONCLUSIONS: Melatonin exerted hepatic immunomodulating changes, in addition to proapoptotic and antiangiogenic effects, illustrated by increased IL-2, caspase-3, and decreased VEGF levels, respectively. Moreover, the use of melatonin during hepatocarcinogenesis positively modulated the disrupted expression of microRNA let7b and Wnt/β-catenin significantly.

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

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Bacterial vaginosis (BV) is a recurrent condition that affects millions of women worldwide. The use of probiotics is a promising alternative or an adjunct to traditional antibiotics for BV prevention and treatment. However, current administration regimens often require daily administration, thus contributing to low user adherence and recurrence. Here, electrospun fibers were designed to separately incorporate and sustain two lactic acid producing model organisms, Lactobacillus crispatus (L. crispatus) and Lactobacillus acidophilus (L. acidophilus). Fibers were made of polyethylene oxide and polylactic-co-glycolic acid in two different architectures, one with distinct layers and the other with co-spun components. Degradation of mesh and layered fibers was evaluated via mass loss and scanning electron microscopy. The results show that after 48 h and 6 days, cultures of mesh and layered fibers yielded as much as 10 and 10 CFU probiotic/mg fiber in total, respectively, with corresponding daily recovery on the order of 10 CFU/(mg·day). In addition, cultures of the fibers yielded lactic acid and caused a significant reduction in pH, indicating a high level of metabolic activity. The formulations did not affect vaginal keratinocyte viability or cell membrane integrity in vitro. Finally, mesh and layered probiotic fiber dosage forms demonstrated inhibition of Gardnerella, one of the most prevalent and abundant bacteria associated with BV, respectively resulting in 8- and 6.5-log decreases in Gardnerella viability in vitro after 24 h. This study provides initial proof of concept that mesh and layered electrospun fiber architectures developed as dissolving films may offer a viable alternative to daily probiotic administration.

Ochradenus baccatus Delile (Resedaceae) is a desert plant with edible fruits native to the Middle East. Few investigators have reported antibacterial, antiparasitic and anti-cancer activities of the plant. Herein we evaluated the cytotoxic activity of O. baccatus using four cell lines and a zebrafish embryo model. Additionally, liquid chromatography coupled with mass spectroscopy was performed to characterize the extract's main constituents. The highest cytotoxicity was observed against human cervical adenocarcinoma (HeLa), with CC of 39.1 µg/mL and a selectivity index (SI) of 7.23 (p < 0.01). Metabolic analysis of the extract resulted in the annotation of 57 metabolites, including fatty acids, flavonoids, glucosinolates, nitrile glycosides, in addition to organic acids. The extract showed an abundance of hydroxylated fatty acids (16 peaks). Further, 3 nitrile glycosides have been identified for the first time in Ochradenus sp., in addition to 2 glucosinolates. These identified phytochemicals may partially explain the cytotoxic activity of the extract. We propose O. baccatus as a possible safe food source for further utilization to partially contribute to the increasing food demand specially in Saharan countries.

BACKGROUND: Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/ sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's Disease (BD) remains unclear.

AIMS: The aim was to determine the frequency of MetS among BD patients and to study its relationship with disease characteristics.

METHODS: The study included 1028 adult BD patients recruited from 18 specialized rheumatology centers. 51 healthy matched control were considered. Behçet Disease Current Activity Form (BDCAF) and the BD damage index (BDI) were estimated. Adult Treatment Panel-III criteria were used to define MetS.

RESULTS: The mean age of patients was 36.8 ± 10.1 years, M:F 2.7:1 and disease duration 7.01 ± 5.2 years. Their mean BDCAF was 5.1 ± 4.6 and BDI 5.5 ± 2.8. MetS was present in 22.8% of patients and in 5.9% of control (3.9 fold higher-risk). Patients with MetS had a significantly increased age at onset (31.8 ± 9.2 vs. 29 ± 8.5 years) and higher frequency of genital ulcers (96.2% vs. 79.7%), skin involvement (73.1% vs. 50.4%), arthritis (48.3% vs. 29.1%) (p<0.0001) and CNS manifestations (18.8% vs. 13%) (p=0.042) compared to those without it. Eye involvement was significantly increased in those with MetS (82.1% vs. 74.2%) (p=0.003) with increased frequency of posterior uveitis (67.1% vs. 43.5%), retinal vessel occlusion (35.9% vs. 21.3%), retinal vasculitis (41.9% vs. 26.4%) (p<0.0001) and vitritis (37.2% vs. 24%) (p=0.001). BDCAF was significantly lower (3.9 ± 4.3 vs. 5.6 ± 4.6) and BDI higher (7.4 ± 2.7vs5 ± 2.6) (p<0.0001).

CONCLUSION: BD patients with MetS are predisposed to mucocutaneous, musculoskeletal, neuropsychiatric and ocular manifestations with consequently increased damage. The involvement of the deeper structures of the eye should alarm rheumatologists to keep in mind that all patients should have an eye examination, especially those with MetS.