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In this study, we aimed to investigate the efficacy and safety of combined fractional carbon dioxide laser and topical timolol maleate 0.5% solution versus topical timolol maleate 0.5% solution alone in inflammatory acne. Thirty adult patients with inflammatory facial acne were randomized in this study. The patients received 3 biweekly sessions of fractional CO2 laser on one side of the face followed by topical timolol maleate ophthalmic solution 0.5% once daily for 7 days on both sides. Outcome was evaluated 2 weeks after the first session, 2 weeks after the last session, and 1 month after the last session by lesion count, erythema, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction. Side effects were also evaluated. Trial registration (IRB No. 417, 30/10/2023). At 2 weeks after the first session, there were insignificant differences between both sides regarding lesion count, erythema, hyperpigmentation, and qualitative global scarring grading ( p value = 0.8, 0.05, 0.7, 0.1 respectively). At 2 weeks after the last session, the erythema on the combined side was reduced by a mean of 0.2 ± 0.4 SD compared to timolol only side with significant difference between both sides ( p value = 0.03), while there were insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction ( p value = 0.1, 0.5, 0.8, 0.3 respectively). Recurrence was detected at one month after the last session. No side effects were reported. Combined fractional CO2 laser and topical timolol maleate 0.5% solution were significantly more effective than topical timolol maleate 0.5% solution alone in reduction of erythema of inflammatory facial acne in adolescent men with Fitzpatrick’s skin type III-IV at 2 weeks after 3 biweekly sessions with insignificant differences between both sides regarding lesion count, hyperpigmentation, qualitative global scarring grading, and patients’ satisfaction. Further and larger studies are still needed.

Hepatocellular carcinoma (HCC) is a highly fatal form of liver cancer. Recently, the interest in using amino acids as therapeutic agents has noticeably grown. The present work aimed to evaluate the possible antiproliferative effects of selected amino acids supplementation or deprivation in human HCC cell lines and to investigate their effects on critical signaling molecules in HCC pathogenesis and the outcomes of their combination with the histone deacetylase inhibitor vorinostat. HepG2 and Huh7 cells were treated with different concentrations of l -leucine, l -glutamine, or l -methionine and cell viability was determined using MTT assay. Insulin-like growth factor 1 (IGF1), phosphorylated ribosomal protein S6 kinase (p70 S6K), p53, and cyclin D1 (CD1) protein levels were assayed using ELISA. Caspase-3 activity was assessed colorimetrically. l -leucine supplementation (0.8–102.4 mM) and l -glutamine supplementation (4–128 mM) showed dose-dependent antiproliferative effects in both cell lines but l -methionine supplementation (0.2–25.6 mM) only affected the viability of HepG2 cells. Glutamine or methionine deprivation suppressed the proliferation of HepG2 cells whereas leucine deprivation had no effect on cell viability in both cell lines. The combination between the effective antiproliferative changes in l -leucine, l -glutamine, and l -methionine concentrations greatly suppressed cell viability and increased the sensitivity to vorinostat in both cell lines. The growth inhibitory effects were paralleled with significant decreases in IGF-1, phospho p70 S6k, and CD1 levels and significant elevations in p53 and caspase-3 activity. Changes in amino acids concentrations could profoundly affect growth in HCC cell lines and their response to epigenetic therapy.

One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-κB inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-κB, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 μM for BEZ-235, 250 μM for DIO) or in combination-2 (0.51 μM for BEZ-235 + 101.99 μM for DIO) inhibited the PI3K/Akt/mTOR/NF-κB axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-II and P62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity. Graphic abstract

Hepatocellular carcinoma (HCC) is still a leading cancer killer in the community. Molecular targeted therapy with celecoxib (CXB) has shown promising antitumor effects; however, its use may be limited due to serious side effects. Curcumin (CUR) has also shown beneficial effects against HCC. Then, it was aimed to investigate the effects of adding CUR to CXB on HCC HepG2 cells. HepG2 cells were treated with CXB and/or CUR at increasing concentrations to investigate synergistic drug interactions, as calculated combination index (CI). Combination treatment effects on cell viability and caspase-3 activation were assessed. The levels of Akt, nuclear factor-kappa B (NF-κB), prostaglandin E2 (PGE2), malondialdehyde (MDA), cyclin D1 (CD1), and vascular endothelial growth factor (VEGF) were also evaluated. CXB (3.13–100 μM) and/or CUR (1.25–40 μM) reduced HepG2 cell viability dose-dependently. Nevertheless, lower combined concentrations showed higher synergism (CI < 1) and higher CXB dose reduction index (DRI > 1). Also, the addition of CUR to CXB resulted in increased cytotoxicity and caspase-3 activation, as compared to CXB alone. In addition, the selected combination significantly reduced the levels of Akt, NF-κB, PGE2, MDA, CD1, and VEGF, as compared to either agent alone. In conclusion, CUR augmented the CXB-mediated antitumor effects in HepG2 cells through, at least in part, antiproliferative, antioxidant, and pro-apoptotic mechanisms. This may allow the further use of CXB at lower concentrations, combined with CUR, as a promising safer targeted strategy for HCC management.

Bee venom (BV) is widely used as a traditional China medicine to treat various conditions, including rheumatoid arthritis (RA). The aim of the present study was to evaluate the effects of systemic BV (60 mg/kg) as an anti-arthritic natural product, compare it with Methotrexate and determine the possible underlying mechanisms of BV action using complete Freund's adjuvant-induced arthritic rats. The development of signs of RA signs (knee joint circumference and arthritis scoring index) was evaluated. Erythrocyte sedimentation rate, serum tumor necrosis factor-α (TNF-α) and serum interleukin-1β (IL-1β) levels were measured at the end of the study. Histopathological examination followed by immunostaining of NF-κB (P65) was performed on the affected knee joints. Additionally, in vitro cyclooxygenase (COX) inhibition activity, carrageenan paw edema test and acetic acid writhing tests were performed to evaluate the anti-inflammatory and analgesic effects of the assessed dose and compared with diclofenac. An acute toxicity test was performed to establish the safety of BV at high doses. The results of the present study highlighted the potential of systemic BV on preventing the development of signs of RA. BV also significantly reduced serum levels of TNF-α, IL-1β and NF-κB in the affected joints. In addition to its potent analgesic activity, BV exhibited favorable inhibitory activity of the COX pathway in both in vivo and in vitro models. Therefore, high dose administration of systemic BV displayed safe and promising anti-arthritic, anti-inflammatory and analgesic properties through regulation of different mechanisms associated with the pathogenesis of RA.