Background and Objectives: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. Materials and Methods: Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. Results: Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11b^high THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DR^low and CD206^low), M1 (HLA-DR^high and CD206^low), and M2 (HLA-DR^low and CD206^high), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. Conclusions: We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.

Background: Mustard honey, a monofloral honey derived from mustard flower is considered a great source of nutritional and medicinal values. The honey is traditionally used as ethnomedicine in different parts of the world to cure many health problems. The present study aimed to evaluate its sedative-anxiolytic potential by integrating three conventional methods in a sequential order.Methods: Open field, hole cross and elevated plus maze experiments were performed in a row with a single oral administration of honey to the Swiss Albino mice. Behavioral parameters like square crossing, rearing, grooming, hole crossing and entry/duration in open arm were observed for each animal in different time intervals. Results: The findings were compared to that of a standard drug, diazepam (1 mg/kg). Mustard honey at higher doses showed sedative activity (4 g/kg and 6 g/kg) whereas with low doses (2 g/kg) exhibited anxiolytic potential. The physicochemical properties of honey were also screened in this study.Conclusions: The integrated method proved to be an effective approach for assessment of neuropharmacological potential for crude or standard medicine. However, further analysis was recommended to investigate active compound which may lead to a new drug development.

As a scaffolding protein, Raf kinase binding protein (RKIP) is involved in a variety of cellular pathways, including the Raf–MEK–ERK-cascade. It acts as a negative regulator by binding to its partners, making it an attractive target in the development of therapeutic strategies for cancer. Despite its structural stability as a monomer, RKIP may form a dimer, resulting in the switching of binding partners. It is still unclear how RKIP switches between monomeric and dimeric forms. Here, we identified the role of cysteine 133 in RKIP structural dynamics using recombinant human RKIP (rhRKIP) proteins purified from Escherichia coli BL21(DE3) cells. Mutation of alanine or serine instead of cysteine in RKIP proteins did not affect the biochemical characteristics, while dynamic light scattering and liquid chromatography (LC) quadrupole time-of-flight (Q-TOF) mass spectrometry (MS) suggested distinct peaks in solution, which were identified via LC–MS/MS analyses, and further clarified the role of cysteine in RKIP dimerization. rhRKIP dimer formation was abrogated by a 32-aa peptide mimicking the region between two RKIP proteins for dimerization. In addition, the 32-aa peptide and its short derivatives were investigated for effects on cancer cell viability. Taken together, our findings suggest that it may be possible to regulate RKIP function by controlling its dynamics with reducing agents, which could aid the targeting of cancer cells.

Background: A search for novel anxiolytic agents has been the prime target for neuroscientists as the currently available treatment methods have certain limitations like physiological dependence, delayed efficacy and side effects. However, naturally occurring agents are raising hopes. The present study was aimed to evaluate the effects of Ziziphus jujube honey over stress related anxiety behavior in Swiss Albino mice. Methods: Following Jujube honey administration (at 2g/kg, 4g/kg and 6g/kg; body weight), the experimental mice were employed in open field and hole-cross test apparatus to evaluate neurologic properties and the anxiolytic activities were investigated using elevated plus maze test (EPM). Mice behavior were observed through parameters of square crossing, rearing, grooming, hole crossing, entry and duration in open arm at different time intervals. Results: At higher doses (6g/kg), Jujube honey was found to possess mild sedative-anxiolytic activity whereas in lower doses (2g/kg & 4g/kg), a non-sedative; anxiolytic potential was observed. Diazepam was effective enough to reduce the locomotor activity and anxiety in all the experiments specially at late phases. Conclusion: The results demonstrated that the anti-anxiety potential of Jujube honey is dose dependent and could be utilized in broad spectrum in inducing sedation and reducing anxiety in mice. Therefore, jujube honey potentiates scopes for further research as a CNS agent.

Background: Honey, derived from different botanical sources, have already been reported for the scientific basis of their antibacterial efficacy, however, varied to a great extent when sourced from different geographical locations. Thus, this study was aimed to highlight the antibacterial potential of honey derived from Bangladesh, Germany and Australia as well as to assess their potency to enhance the efficacy of standard antibiotics against resistant bacteria. Methods: In vitro susceptibility of four resistant gram-positive bacterial strains to honey samples and their combinations with standard antibiotics (penicillin and amoxiclav) were investigated. The evaluation of antibacterial activity was performed by disc diffusion method as well as microdilution method using two-fold dilutions of honey samples ranging from 12.5µg/ml to 0.78µg/ml. Zone of inhibition, percentage inhibition, MIC and MBC were observed in this regard. Results: The results revealed that tested honey samples exhibited noticeable antibacterial activity against the bacterial strains. Maximum inhibition zone was observed by Bangladeshi honey (20.4mm) against M. luteus and highest inhibition percentage was demonstrated by German honey against B. subtilis (82%). Combinations with amoxiclav showed nearly two-fold increase in efficacy by all honeys, when treated against all species. Conclusion: The findings from this study suggested that, in addition to having inhibitory effects, all honey also enhanced the pharmacological action of penicillin and amoxiclav and could generate a potential research focus to establish a supplement for these antibiotics.