Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC

Retinoid Therapy in a Case of Harlequin Ichthyosis with a Short Literature Review

Harlequin ichthyosis (HI) is a genetically inherited epidermal disorder due to the mutation of the ABCA12 gene, which is responsible for lipid transportation, and presents with large keratinised scales characterised by deep erythematous fissures, with ectropion and eclabium. A moderate number of cases and a high mortality rate have been recorded. In this case report, a pregnant lady gave birth to a 33-week-old premature foetus with characteristic symptoms of HI. After admitting him to the NICU, a multidisciplinary treatment approach was conducted with paediatric dermatologists, ophthalmologists, urologists, and dieticians. The prognosis is positive, with desquamation of the hyperkeratotic plate revealing an erythematous and shiny skin. A short literature review on HI characteristics, diagnostic aids, and management has also been added

Evaluation of the Anticancer Potential of Crude, Irradiated Cerastes cerastes Snake Venom and Propolis Ethanolic Extract & Related Biological Alterations

We aimed to evaluate the anticancer potential of crude venom (CV), γ irradiated Certastes cerastes venom (IRRV), and propolis ethanolic extract (PEE). IRRV showed a higher toxicity than CV, while CV-PEE showed higher toxicity than IRRV and CV against lung [A549] and prostate [PC3] cancer cells. Toxicity to [A549] and [PC3] cells was concentration and cell type dependent. In comparison to controls, apoptotic genes showed a significant upregulation of P53 and Casp-3 and a downregulation of Bcl-2. Also, induced elevated DNA accumulation in the [S] phase post PC3 cell treatment with IRRV and CV, as well as a significant DNA accumulation at G2/M phase after IRRV treatment of A549 cells. In contrast, PC3 cells showed a negligible cellular DNA accumulation after PEE treatment. Glutathione reductase [GR] was reduced in case of PC3 and A549 cell treated with IRRV, CV, and PEE compared with its values in untreated cell control. The Malondialdehyde [MDA] values in both cells recorded a significant elevation post IRRV treatment compared to the rest of the treatment regimen and untreated cell control. Similarly, IRRV and CV-PEE mix showed obviously higher reactive oxygen species [ROS] values than PC3 and A549 cell treatments with CV and PEE

Synthesis and cytotoxic activity of new indolylpyrrole derivatives

The current approach described the synthesis of a new series of indolylpyrrole derivatives through multicomponent reaction of α-cyano chalcones, appropriate aldehydes, and ammonium acetate in refluxed acetic acid. The chemical structures of the designed compounds were confirmed with spectroscopic data and elemental analysis and then tested for their in vitro cytotoxic activity by SRB assay method towards three cell lines involving human Prostate adenocarcinoma; metastatic cells (PC-3), human ovary adenocarcinoma (SKOV3) and human dukes' type B, colorectal adenocarcinoma (LS 174 T). Most significant activity provided with compounds 5c, 5h and, 5j against prostate cancer cells (PC-3) with IC50s of 3.30 ± 0.20, 3.60 ± 0.10, and 3.60 ± 0.90 µg/ml, respectively. In human ovarian carcinoma (SKOV3), the compounds 5a, and 5i have stronger cytotoxicity with IC50s of 1.20 ± 0.04, 1.90 ± 0.50 µg/ml, respectively than the standard doxorubicin (IC50 = 2.20 ± 0.02 µg/ml). On the other hand, only compound 5a has the ability to diminish the viability of LS174T cells in an active manner with IC50 2.80 ± 0.10 µg/ml. Consequently, this effort offers groundwork for additional examination of nominated indolylpyrroles as antiproliferative agents

Floristic Diversity and Phytogeography of JABAL Fayfa: A Subtropical Dry Zone, South-West Saudi Arabia

The present study surveyed the flora of the Jebel Fayfa region, South-West Saudi Arabia to analyze four elements of the vegetation: floristic diversity, life form, lifespan, and phytogeographical affinities. A total of 341 species of vascular plants were recorded belonging to 240 genera in 70 families, of which 101 species distributed among 40 families were considered as new additions to the flora of Jabal Fayfa. Six species are considered endemic to the study area while 27 are endangered. The most represented families were Fabaceae, Asteraceae, and Poaceae. The flora of Jabal Fayfa exhibited a high degree of monotypism. A total of 20 families (28.57%) were represented by a single species, and 180 genera (75.00%) were monotypic. The recorded flora consists of 70.09% perennials and 29.91% annuals. Phanerophytes and therophytes were the most frequent lifeforms. Phytogeographical analysis revealed that the biregional elements of the Saharo-Arabian/Sudano-Zambezian chorotype are the most dominant chorotypes (35.48%), forming two-thirds of the floristic structure in Jabal Fayfa. The new additions to the local flora of the region indicate that the Jabal Fayfa region and the country need further thorough botanical exploration and documentation which would help in adding several species to the flora of Saudi Arabia

Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway

Background. Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. Results. In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 μg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 μg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. Conclusion. These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver

Black widow spider (Latrodectus renivulatus) envenomation in children in Saudi Arabia: a case series

AbstractBlack widow spider (Latrodectus renivulatus) envenomation is a toxicological emergency affecting Middle Eastern countries. Young children may experience greater morbidity due to their small size relative to the amount of venom delivered. We describe four pediatric cases of severe black widow spider envenomation in Saudi Arabia. The neurological effects predominated, and all patients needed morphine for pain relief. All patients required admission to the pediatric intensive care unit (PICU). The durations of PICU stay and total hospital stay were 1–3 days and 2–5 days, respectively. Although Latrodectus antivenom is safe and effective, Latrodectus antivenom was unavailable, and no patients received antivenom. We believe that Latrodectus antivenom would rapidly relieve symptoms and shorten hospital stays

L-Glutaminase Synthesis by Marine Halomonas meridiana Isolated from the Red Sea and Its Efficiency against Colorectal Cancer Cell Lines

L-glutaminase is an important anticancer agent that is used extensively worldwide by depriving cancer cells of L-glutamine. The marine bacterium, Halomonas meridian was isolated from the Red Sea and selected as the more active L-glutaminase-producing bacteria. L-glutaminase fermentation was optimized at 36 h, pH 8.0, 37 °C, and 3.0% NaCl, using glucose at 1.5% and soybean meal at 2%. The purified enzyme showed a specific activity of 36.08 U/mg, and the molecular weight was found to be 57 kDa by the SDS-PAGE analysis. The enzyme was highly active at pH 8.0 and 37 °C. The kinetics’ parameters of Km and Vmax were 12.2 × 10−6 M and 121.95 μmol/mL/min, respectively, which reflects a higher affinity for its substrate. The anticancer efficiency of the enzyme showed significant toxic activity toward colorectal adenocarcinoma cells; LS 174 T (IC50 7.0 μg/mL) and HCT 116 (IC50 13.2 μg/mL). A higher incidence of cell death was observed with early apoptosis in HCT 116 than in LS 174 T, whereas late apoptosis was observed in LS 174 T more than in HCT 116. Also, the L-glutaminase induction nuclear fragmentation in HCT 116 was more than that in the LS 174T cells. This is the first report on Halomonas meridiana as an L-glutaminase producer that is used as an anti-colorectal cancer agent

Sleep-Disordered Breathing and Its Association with Nocturnal Enuresis at the Primary Schools in Saudi Arabia: A Cross-Sectional Study

The correlation between nocturnal enuresis (NE) and sleep-disordered breathing (SDB) was reported. We aim to determine whether there is an association between NE and SDB in children and to assess the prevalence of SDB and NE in primary school children aged 6–12 years in Saudi Arabia. A cross-sectional observational study was conducted among the caregivers of children aged 6–12 years in all Saudi Arabia regions. The data were gathered through a self-administered online questionnaire. It included demographic information, weight and height, and associated comorbidities, in addition to the weekly frequencies of snoring symptoms and of enuresis, as well as of unrefreshing sleep using Likert-type response scales. Counts and percentages, the mean ± standard deviation, chi-square test, independent samples t-test, and regression analysis were used in the statistical analysis using R v 3.6.3. The questionnaire was completed by 686 respondents. Most respondents did not report any comorbidities in their children (77.1%). Asthma and adenotonsillar hypertrophy were reported in 16.2% and 15.6% of children, respectively. Unrefreshing sleep, mouth breathing at night, snoring, chronic nasal obstruction, and difficulty breathing while asleep were reported once or twice per week in 38%, 34%, 28%, 18%, and 18% of children, respectively. The prevalence of NE was 22.3%, with about 36.6% of children having NE two or more times per week. Significantly, NE was reported in 26.6% of children who slept before 10 PM compared to 19% of children who slept after 10 PM; in 28.6% of children who snored or loudly snored (57.1%) three times or more per week; and in 51.2% and 27.5% of children with difficulty breathing while asleep and who breathed through their mouth at night for one or two nights per week, respectively. A multivariable regression analysis showed that male gender (OR = 1.52, p = 0.010), obesity (OR = 1.24, p = 0.028), early sleeping time (OR = 1.40, p = 0.048), loud snoring for three or more nights per week (OR = 1.54, p = 0.001), difficulty breathing for one or two nights per week (OR = 1.85, p = 0.010), and mouth breathing at night for one or two nights per week (OR = 1.55, p = 0.049) were associated with higher odds of NE. Our study revealed that 22.3% of primary school children reported suffering from NE. SDB is a common problem among children with NE. The exact mechanism that links SDB to the increase in the risk of NE is unknown. Male gender, obesity, early sleeping time, loud snoring, difficulty breathing, and mouth breathing at night are potential independent risk factors of NE in school-age children

The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design : An In Vivo and In Vitro Approach

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 +/- 1.13), while a maximum of 92.87 +/- 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 mu m. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t1/2) of 4.54 +/- 0.18 h and a C-max of 128 +/- 0.87 (ng/mL); T-max was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively