Thymoquinone (TQ) is the active ingredient of Nigella sativa which has a therapeutic potential in cancer therapy and prevention. In this study, TQ has been shown to induce specific cytotoxicity and apoptosis and to inhibit wound healing in triple-negative breast cancer cell line. TQ also inhibited cancer growth in a mouse tumor model. Moreover, TQ and paclitaxel (Pac) combination inhibited cancer growth in cell culture and in mice. Genes involved in TQ and TQ-Pac-mediated cytotoxicity were studied using focused real-time PCR arrays. After bioinformatic analysis, genes in apoptosis, cytokine, and p53 signaling categories were found to be modulated with a high significance in TQ-treated cells (p < 10(-28), p < 10(-8), and p < 10(-6), respectively). Important to note, TQ has been found to regulate the genes involved in the induction of apoptosis through death receptors (p = 5.5 × 10(-5)). Additionally, tumor suppressor genes such as p21, Brca1, and Hic1 were highly upregulated by TQ and TQ-Pac combination. Interestingly, when cells were treated with high dose TQ, several growth factors such as Vegf and Egf were upregulated and several pro-apoptotic factors such as caspases were downregulated possibly pointing out key pathways manipulated by cancer cells to resist against TQ. In cells treated with the combination of TQ and Pac, genes in apoptosis cascade (p < 10(-12)), p53 signaling (p = 10(-5)), and JAK-STAT signaling (p < 10(-3)) were differentially expressed. TQ has also been shown to induce protein levels of cleaved Caspase-3, Caspase-7, and Caspase-12 and PARP and to reduce phosphorylated p65 and Akt1. The in vivo therapeutic potential of TQ-Pac combination and the genetic network involved in this synergy have been shown for the first time to the best of our knowledge.

Sphingosine-1 phosphate receptor 1 (S1PR1) is expressed by lymphocytes and regulates their egress from secondary lymphoid organs. Innate lymphoid cell (ILC) family has been expanded with the discovery of group 1, 2 and 3 ILCs, namely ILC1, ILC2 and ILC3. ILC3 and ILC1 have remarkable similarity to CD4+ helper T cell lineage members Th17 and Th1, respectively, which are important in the pathology of multiple sclerosis (MS). Whether human ILC subsets express S1PR1 or respond to its ligands have not been studied. In this study, we used peripheral blood/cord blood and tonsil lymphocytes as a source of human ILCs. We show that human ILCs express S1PR1 mRNA and protein and migrate toward S1P receptor ligands. Comparison of peripheral blood ILC numbers between fingolimod-receiving and treatment-free MS patients revealed that, in vivo , ILCs respond to fingolimod, an S1PR1 agonist, resulting in ILC-penia in circulation. Similarly, murine ILCs responded to fingolimod by exiting blood and accumulating in the secondary lymph nodes. Importantly, ex vivo exposure of ILC3 and ILC1 to fingolimod or SEW2871, another S1PR1 antagonist, reduced production of ILC3- and ILC1- associated cytokines GM-CSF, IL-22, IL-17, and IFN-γ, respectively. Surprisingly, despite reduced number of lamina propria-resident ILC3s in the long-term fingolimod-treated mice, ILC3-associated IL-22, IL-17A, GM-CSF and antimicrobial peptides were high in the gut compared to controls, suggesting that its long term use may not compromise mucosal barrier function. To our knowledge, this is the first study to investigate the impact of fingolimod on human ILC subsets in vivo and ex vivo , and provides insight into the impact of long term fingolimod use on ILC populations.

We investigated whether a proximal femoral nail (PFN) having two lag screws can be implanted without distal locking screws in AO/OTA 31-A1 and 31-A2 intertrochanteric femur fractures. Twenty-four patients with AO/OTA 31-A1 and 31-A2 fractures were treated with a PFN without distal interlocking by a single surgeon. The mean follow-up was 12 months (range: 7-23). Clinical and functional outcome was assessed according to the Harris hip score and Barthel's activity score. The fractures healed in all patients; the average consolidation time was 14 weeks (range: 9-28). Fourteen patients had excellent and good results, nine patients had fair results, and one patient had a poor result according to the Harris hip score; 17 patients had a high range of mobility according to the Barthel activity score. Our results suggested that the PFN can be successfully implanted without distal interlocking in 31-A1 and 31-A2 fractures.

An adenomatoid odontogenic tumor is an uncommon asymptomatic lesion that is often misdiagnosed as a dentigerous cyst. It originates from the odontogenic epithelium. Enucleation and curettage is the usual treatment of choice. Marsupialization may be attempted instead of extraction of the impacted tooth, since it provides an opportunity for tooth eruption. This case report is the first to report on the eruption of an impacted canine in an adenomatoid odontogenic tumor treated with combined orthodontics and marsupialization. The impacted canine erupted uneventfully, with no evidence of recurrence 3 years after the treatment.

Myrtucommulone-A is the active compound derived from Myrtus communis. The molecular targets of myrtucommulone-A is widely unknown, which impedes its potential therapeutic use. In this study, we demonstrated the cytotoxicity of MC-A and its potential to induce apoptosis in cancer cells. Myrtucommulone-A was also found to be antiproliferative and strongly inhibited cancer cell migration. Eighty four apoptotic pathway genes were used to assess the effect of myrtucommulone-A on cancer cells. Myrtucommulone-A mediated an increase in apoptotic genes including Fas, FasL, Gadd45a, Tnf, Tnfsf12, Trp53, and caspase 4. The increase in myrtucommulone-A dose (25 μM versus 6.25 μM) also upregulated the expression of genes, which are involved mainly in apoptosis, regulation of apoptosis, role of mitochondria in apoptotic signaling, cytokine activity, and tumor necrosis factor signaling. Our data indicate that myrtucommulone-A could be utilized as a potential therapeutic compound with its molecular targets in apoptotic pathways.