Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments.

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 µg/mL, compared to celecoxib drug (IC50 value 251.2 µg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1ß. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 µg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.

Effect of Ducrosia flabellifolia and Savignya parviflora Extracts on Inhibition of Human Colon and Prostate Cancer Cell Lines.

The goal of this study was to investigate whether Ducrosia flabellifolia and Savignya parviflora methanol extract the have effect on colon and prostate cancer cell lines. Analysis of total content of phenolics and flavonoids of each plant extract was carried out. Cytotoxic effect, cell cycle analysis, induction of apoptosis and gene expression of Bcl-2 and Bax genes were studied. Obtained results indicated that, the plant extracts exhibit growth inhibition of used cancer cell lines and induced apoptosis as well as arresting of cell cycle. At the molecular level, changes in gene expression were detected via qPCR and confirmed by western blotting. The exhibited anticancer potentialities of plant extracts against utilized cancer cell lines are due to its containing bioactive compounds. Further detailed isolation, fractionation and characterization of bioactive compounds are needed.

Comparative efficacy of Gum Arabic (Acacia senegal) and Tribulus terrestris on male fertility.

In this study the effect of Gum arabic (Acacia Senegal) was systemically targeted at male fertility with two experiments, the first comparing the effectiveness of Gum arabic (GA) and Tribulus terrestris (TT). For the first experiment, 27 adult mice Balb / c (18 females, 9 males) were divided into 3 in each group, one male and two females, group one had the usual tap water as power, group two had 5% (w / v) GA and group three had 5% (w / v) of TT for 21 days. The results showed, the number of offspring was more with GA treated when compared to TT treated. Blood measurements of testosterone showed significant increase in the GA group as compared to other groups, also Histopathological analysis showed the dose dependent 5% GA had normal seminiferous tubules with increase spermatogenesis. In this study the enhanced fertility in GA-treated mice Balb/c was observed and the experimental studies also show that GA fertility was increased.

Coexistence of Lichen Planus Pigmentosus and Classic Lichen Planopilaris: A Case Report and Literature Review.

Lichen planus (LP) is a common inflammatory skin disorder with multiple variants. The coexistence of lichen planus pigmentosus (LPPigm) and frontal fibrosing alopecia is well-established in the literature. However, the coexistence of LPPigm and classic lichen planopilaris (LPP) is rare. We report a case of LPPigm and classic LPP in a postmenopausal woman with a literature review.

Independent case-control study in KCNJ11 gene polymorphism with Type 2 diabetes Mellitus.

Background: Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes in the aging population. This chronic metabolic disorder has discovered many candidate genes, and KCNJ11 was one of the genes associated with insulin secretion pathways mediated by potassium channels. There have been limited studies on the rs5210 polymorphism in T2DM patients, and none of them have been conducted in Saudi Arabia. Aim: The aim of this study is to investigate at genotyping levels of rs5210 polymorphism in the KCNJ11 gene in older population with T2DM in the Saudi Population. Methods: Based on the sample size design, this case-control study included 102 T2DM cases and 102 controls. Using the PCR-RFLP assay, 204 patients extracted DNA was genotyped for the rs5210 polymorphism. SPSS software was used for statistical analysis, including t-tests, HWE, genotyping, and multiple logistic regression analysis. Results: The t-tests performed on T2DM cases and controls revealed a significant association in age, weight, BMI, FBG, Hb1Ac, SBP, DBP, HDLC, TC, and TG parameters (p < 0.05). HWE analysis found to be in consistent with rs5210 polymorphism. Allelic association was found in the rs5210 polymorphism (OR-1.64 [95 %CI: 1.08-2.49]; p = 0.01); however, no association (p > 0.05) was observed in the multivariate logistic regression assessment performed in this study. Conclusion: These results indicate that the rs5210 polymorphism was primarily associated with allele frequencies, which could be attributable to the small sample size. Large sample size studies will be required to determine whether KCNJ11 gene polymorphisms may be required as a risk marker for T2DM in the Saudi population.

Topical Corticosteroid-Induced Adrenal Insufficiency: A Case Report.

Topical Corticosteroids (TCS) are the most commonly prescribed medications in Dermatology practice. They are considered safe and effective if used at the appropriate location and for the appropriate duration. Local side effects due to TCS are not uncommon. However, systemic side effects are rare. Herein, we present a patient who developed adrenal insufficiency secondary to the use of TCS.

Herpetic Whitlow of the Hand in Infants.

Introduction Herpetic whitlows in infants are rare. Previous authors only reported individual case reports. We present a case series of six infants. Materials and Methods This is a retrospective study of six cases of herpetic whitlows in infants seen by the senior author (MMA) over the past 23 years (1995-2017 inclusive). The following data were collected: age, sex, digit involved in the hand, mode of transmission, time of presentation to the author, clinical appearance, presence of secondary bacterial infection, presence of other lesions outside the hand, method of diagnosis, treatment, and outcome. Results All six infants initially presented with classic multiple vesicles of the digital pulp. In all cases, there was a history of active herpes labialis in the mother. Incision and drainage or deroofing of the vesicles (for diagnostic purposes) resulted in secondary bacterial infection. Conclusion The current report is the first series in the literature on herpetic whitlows in infants. We stress on the mode of transmission (from the mother) and establishing the diagnosis clinically. In these cases, no need for obtaining viral cultures or polymerase chain reaction; and no medications are required. Once the vesicles are disrupted, secondary bacterial infection is frequent and a combination of oral acyclovir and intravenous antibiotics will be required.

Exploring the Interactive Effects of Thymol and Thymoquinone: Moving towards an Enhanced Performance, Gross Margin, Immunity and Aeromonas sobria Resistance of Nile Tilapia (Oreochromis niloticus).

Plant-derived bioactive compounds with promising nutritional and therapeutic attributes (phytogenics) are among the top priorities in the aquaculture sector. Therefore, the impact of thymol (Thy) and/or thymoquinone (ThQ) on the growth, immune response antioxidant capacity, and Aeromonas sobria (A. sobria) resistance of Nile tilapia was investigated. Four fish groups were fed a control diet and three basal diets supplemented with 200 mg/kg diet of Thy or ThQ and a blend of both Thy and ThQ at a level of 200 mg/kg diet each. At the end of the feeding trial (12 weeks), the tilapias were challenged intraperitoneally with virulent A. sobria (2.5 × 108 CFU/mL) harboring aerolysin (aero) and hemolysin (hly) genes. The results revealed that tilapias fed diets fortified with a combination of Thy and ThQ displayed significantly enhanced growth rate and feed conversion ratio. Notably, the expression of the genes encoding digestive enzymes (pepsinogen, chymotrypsinogen, α-amylase and lipase) and muscle and intestinal antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase) was significantly upregulated in Thy/ThQ-fed fish. An excessive inflammatory response was subsided more prominently in the group administrated Thy/ThQ as supported by the downregulation of il-ß, il-6 and il-8 genes and in contrast, the upregulation of the anti-inflammatory il-10 gene. Remarkably, dietary inclusion of Thy/ThQ augmented the expression of autophagy-related genes, whilst it downregulated that of mtor gene improving the autophagy process. Furthermore, Thy/ThQ protective effect against A. sobria was evidenced via downregulating the expression of its aero and hly virulence genes with higher fish survival rates. Overall, the current study encouraged the inclusion of Thy/ThQ in fish diets to boost their growth rates, promote digestive and antioxidant genes expression, improve their immune responses and provide defense against A. sorbia infections with great economic benefits.

Sirolimus in the Management of Blue Rubber Bleb Nevus Syndrome: A Case Report and Review of the Literature.

Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation (VM) that may affect any tissue or organ but mainly affects the skin, subcutaneous tissue and gastrointestinal (GI) tract. Patients present with serious anemia, treated with lifelong iron supplements and frequent blood transfusion secondary to chronic GI bleeding. Variable therapeutic modalities were used in the management of BRBNS; sirolimus (SRL), a mammalian target of rapamycin (mTOR) inhibitor, is found to be a promising therapy for vascular anomalies.

Erythrodermic CD4/CD8 Double-Negative Mycosis Fungoides: A Case Report.

Cutaneous T-cell lymphoma (CTCL) describes a group of lymphoproliferative disorders characterized by localization of neoplastic T lymphocytes to the skin. Mycosis fungoides (MF) represents the most common type of CTCL and accounts for ∼60% of all primary cutaneous lymphomas. Apart from the classic type of MF, many clinical and histopathologic variants have been described. The malignant lymphocytes in MF are usually CD3, CD4 and CD45RO positive and CD8 negative. An unusual immunohistochemical profile of a CD4-negative and CD8-positive mature T-cell phenotype has been reported in a minority of patients; up to 20% of early-stage MF demonstrates a CD8-positive phenotype. There are only a few cases of a double-negative CD4/CD8 MF phenotype reported in the literature. We present the case of a 60-year-old male presenting a double-negative CD4/CD8 MF phenotype.

Intravenous Immunoglobulin in the Management of Lupus Erythematosus Panniculitis.

Lupus erythematosus panniculitis (LEP) is a rare variant of cutaneous lupus erythematosus (CLE). It is characterized by the presence of a chronic inflammatory process involving the deep dermis and subcutaneous tissues. It commonly presents as deep indurated nodules or sharply demarcated plaques. Antimalarial medications are considered first-line therapy for most cases of LEP while systemic corticosteroids are saved for more resistant lesions. Intravenous immunoglobulin (IVIG) is made up of concentrated polyclonal immunoglobulin G (IgG) fractionated from the blood of healthy blood donors. Nowadays, it is used for the treatment of numerous autoimmune and systemic inflammatory diseases. In this case, we report the case of a female with multiple LEP and discoid lupus erythematosus (DLE) lesions refractory to multiple standard therapy modalities that responded dramatically to IVIG.

Transcriptional responses to hyperplastic MRL signalling in Drosophila.

Recent work has implicated the actin cytoskeleton in tissue size control and tumourigenesis, but how changes in actin dynamics contribute to hyperplastic growth is still unclear. Overexpression of Pico, the only Drosophila Mig-10/RIAM/Lamellipodin adapter protein family member, has been linked to tissue overgrowth via its effect on the myocardin-related transcription factor (Mrtf), an F-actin sensor capable of activating serum response factor (SRF). Transcriptional changes induced by acute Mrtf/SRF signalling have been largely linked to actin biosynthesis and cytoskeletal regulation. However, by RNA profiling, we find that the common response to chronic mrtf and pico overexpression in wing discs was upregulation of ribosome protein and mitochondrial genes, which are conserved targets for Mrtf/SRF and are known growth drivers. Consistent with their ability to induce a common transcriptional response and activate SRF signalling in vitro, we found that both pico and mrtf stimulate expression of an SRF-responsive reporter gene in wing discs. In a functional genetic screen, we also identified deterin, which encodes Drosophila Survivin, as a putative Mrtf/SRF target that is necessary for pico-mediated tissue overgrowth by suppressing proliferation-associated cell death. Taken together, our findings raise the possibility that distinct targets of Mrtf/SRF may be transcriptionally induced depending on the duration of upstream signalling.