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  • Clark Hastings posted an update 1 week, 6 days ago

    In all, 25 compounds (mostly terpenes and flavonoids) have been isolated from medicinal plants with wound healing activity; therefore, extensive work is necessary for a multidisciplinary approach to evaluate the wound healing effects of medicinal plants in Latin America. The mechanism of action of medicinal plants, their toxicological actions on the skin, and their bioactive compounds, have yet to be investigated. This review on the ethnomedicinal, phytochemical, and pharmacological studies, of medicinal plants from Latin America with wound healing activity, offers promising data for further studies, as well as providing new insights into their possible role in wound care.Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT.

    Inducing mesenchymal stem cells (MSCs) osteogenesis may be beneficial in a number of clinical applications. The aim of this study is to identify key novel biomarkers of this process and to analyze the possible regulatory effects on inflammation and immunity.

    Seven datasets (GSE159137, GSE159138, GSE114117, GSE88865, GSE153829, GSE63754, GSE73087) were obtained from the Gene Expression Omnibus database and were assigned to either the training or the validation dataset. The least absolute shrinkage and selection operator (LASSO) logistic regression model was applied to the training data to select biomarkers of osteogenesis, which were then confirmed using the validation dataset. FK506 binding protein 5 (FKBP5), insulin-like growth factor binding protein (IGFBP2), prostaglandin E receptor 2 (PTGER2), SAM domain and HD domain-containing protein 1 (SAMHD1), and transmembrane tetratricopeptide 1 (TMTC1) were highlighted as potential biomarkers. In addition, the differential expressions of immunity and inflammation-related genes were examined and their correlations with the five identified biomarkers were analyzed. The results from performing RT-qPCR and Western blots confirmed that the levels of each of these biomarkers were all significantly increased following osteogenic differentiation of MSCs.

    Our results identify five biomarkers related to MSCs osteogenesis and allow us to identify their potential roles in immunoregulation and inflammation. Each biomarker was verified by in vitro experiments.

    Our results identify five biomarkers related to MSCs osteogenesis and allow us to identify their potential roles in immunoregulation and inflammation. Each biomarker was verified by in vitro experiments.Human immunodeficiency virus (HIV) infection is a major problem for humanity because HIV is constantly changing and developing resistance to current drugs. This necessitates the development of new anti-HIV drugs that take new approaches to combat an ever-evolving virus. One of the promising alternatives to combination antiretroviral therapy (cART) is the molecular hybrid strategy, in which two or more pharmacophore units of bioactive scaffolds are combined into a single molecular structure. These hybrid structures have the potential to have higher efficacy and lower toxicity than their parent molecules. Given the potential advantages of the hybrid molecular approach, the development and synthesis of these compounds are of great importance in anti-HIV drug discovery. This review focuses on the recent development of hybrid compounds targeting integrase (IN), reverse transcriptase (RT), and protease (PR) proteins and provides a brief description of their chemical structures, structure-activity relationship, and binding mode.Pharmaceutical compounding is an important component of pharmacy practice despite its low prevalence. Several therapeutic needs can be met by a compounded medicine such as dosing adjusted for pediatric patients, special drug combinations, medicines for patients allergic to a given excipient, and medicines for orphan drugs not provided by the pharmaceutical industry. Examples of such applications are provided in this review. Adherence to medication is a critical public health issue as nonadherence to pharmacotherapy has been associated with adverse outcomes and higher costs of patient care. Adherence to therapy represents a key factor in the reduction in morbidity and mortality and optimization of the use of financial resources. The role of pharmaceutical compounding in promoting medication adherence is underexploited. The customization might represent a positive reinforcement of the initiation of the treatment, while implementation and persistence might also be favored in a pharmacy setting. However, studies addressing the influence of compounding in adherence promotion are lacking in the literature. The results of such studies could support health policies including proper regulatory framework, pharmacist training, and information to health care practitioners.Indoleamine 2, 3-dioxygenase 1 (IDO1) is commonly expressed by cancers as a mechanism for evading the immune system. Preclinical and clinical studies have indicated the potential of combining IDO1 inhibitors with immune therapies for the treatment of cancer, strengthening an interest in the discovery of novel dioxygenase inhibitors for reversing tumour-mediated immune suppression. To facilitate the discovery, development and investigation of novel small molecule inhibitors of IDO1 and its hepatic isozyme tryptophan dioxygenase (TDO2), murine tumour cells were engineered to selectively express either murine or human IDO1 and TDO2 for use as tools to dissect both the species specificity and isoenzyme selectivity of newly discovered inhibitors. Lewis lung carcinoma (LLTC) lines were engineered to express either murine or human IDO1 for use to test species selectivity of the novel inhibitors; in addition, GL261 glioma lines were engineered to express either human IDO1 or human TDO2 and used to test the isoenzyme ective for either TDO2 or IDO1. These results demonstrate the versatility of W-0019482 as a lead in generating all three subclasses of tryptophan dioxygenase inhibitors which can be applied for investigating the individual roles and interactions between IDO1 and TDO2 in driving cancer-mediated immune suppression.Opophytum forsskalii (O. forsskalii) is a desert plant that belongs to the Aizoaceae family. Although it is a natural food source for Bedouin tribes in northern Saudi Arabia, there is little information on its active metabolites. Therefore, the secondary metabolites of the hydroalcoholic extract from the leaves of this species were analyzed by liquid chromatography-mass chromatography (LC-MS). LC-MS identified a total of 30 secondary metabolites. These compounds represented two main categories among sixteen classes. Among them, flavonoids represented the largest proportion with eleven metabolites while fatty acids provided seven compounds. In addition, the extract was evaluated for its gastroprotective effect against gastric lesions induced by different models, such as indomethacin, stress, and necrotizing agents (80% ethanol, 0.2 mol/L NaOH, and 25% NaCl), in rats. For each method, group 1 was used as the control group while groups 2 and 3 received the leaf extract at doses of 200 and 400 mg/kg, respectively. The ulcer index (UI) and intraluminal bleeding score (IBS) were measured for each method. In addition, gastric tissue from the ethanol method was used for the analysis of nonprotein sulfhydrates (NP-SH), malondialdehyde (MDA), total protein (TP), and histopathologic evaluation. Pretreatment with O. forsskalii significantly decreased UI (p < 0.01) and IBS (p < 0.01) at 400 mg/kg. Pretreatment with O. forsskalii significantly improved total protein levels (p < 0.01) and NP-SH (p < 0.001) compared to the ethanol ulcer groups. MDA levels increased from 0.5 to 5.8 nmol/g in the normal groups compared to the ethanol groups and decreased to 2.34 nmol/g in the O. forsskalii pretreatment. In addition to the gastroprotective markers, histopathological examination of gastric tissue confirmed the gastroprotective potential of O. forsskalii extract against ethanol.NADHubiquinone oxidoreductase (respiratory complex I) is a redox-driven proton pump with a central role in mitochondrial oxidative phosphorylation. The ubiquinone reduction site of complex I is located in the matrix arm of this large protein complex and connected to the membrane via a tunnel. A variety of chemically diverse compounds are known to inhibit ubiquinone reduction by complex I. Rotenone, piericidin A, and annonaceous acetogenins are representatives of complex I inhibitors from biological sources. The structure of complex I is determined at high resolution, and inhibitor binding sites are described in detail. In this review, we summarize the state of knowledge of how natural inhibitors bind in the Q reduction site and the Q access pathway and how their inhibitory mechanisms compare with that of a synthetic anti-cancer agent.Retinoblastoma is a rare, sometimes hereditary, pediatric cancer. In high-income countries this disease has a survival rate approaching 100%, while in low- and middle-income countries the prognosis is fatal for about 80% of cases. Depending on the stage of the disease, different therapeutic protocols are applied. K-Ras(G12C) inhibitor 12 In more advanced forms of the disease, surgical removal of the entire globe and its intraocular contents (enucleation) is, unfortunately, necessary, whereas in other cases, conventional chemotherapy is normally used. To overcome the side-effects and reduced efficacy of traditional chemotherapic drugs, nanodelivery systems that ensure a sustained drug release and manage to reach the target site have more recently been developed. This review takes into account the current use and advances of nanomedicine in the treatment of retinoblastoma and discusses nanoparticulate formulations that contain conventional drugs and natural products. In addition, future developments in retinoblastoma treatment are discussed.We characterized the in vitro safety and bioavailability profile of silvestrol, a compound effective against various viruses, such as corona- and Ebolaviruses, with an EC50 value of about 5 nM. The cytotoxic profile of silvestrol was assessed in various cancer cell lines, as well as the mutagenic and genotoxic potential with Ames and micronuclei tests, respectively. To identify off-target effects, we investigated whether silvestrol modulates G-protein coupled receptor (GPCR) signaling pathways. To predict the bioavailability of silvestrol, its stability, permeability and cellular uptake were determined. Silvestrol reduced viability in a cell-type-dependent manner, mediated no off-target effects via GPCRs, had no mutagenic potential and minor genotoxic effects at 50 nM. Silvestrol did not disturb cell barrier integrity, showed low membrane permeability, was stable in liver microsomes and exhibited good cellular uptake. Efficient cellular uptake and increased cytotoxicity were observed in cell lines with a low expression level of the transport protein P-glycoprotein, the known efflux transporter of silvestrol.