Influence of Various Strontium Formulations (Ranelate, Citrate, and Chloride) on Bone Mineral Density, Morphology, and Microarchitecture: A Comparative Study in an Ovariectomized Female Mouse Model of Osteoporosis.

Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.

Pectolinarigenin ameliorates osteoporosis via enhancing Wnt signaling cascade in PPARß-dependent manner.

BACKGROUND: Osteoporosis is a prevalent metabolic bone disease in older adults. Peroxisome proliferator-activated receptor ß (PPARß), the most abundant PPAR isotype expressed in bone tissues, plays a critical role in regulating the energy metabolism of osteoblasts. However, the botanical compounds targeting PPARß for the treatment of osteoporosis remain largely unexplored. PURPOSE: To discover a potent PPARß agonist from botanical compounds, as well as to investigate the anti-osteoporosis effects and to elucidate the underlying mechanisms of the newly identified PPARß agonist. METHODS: The PPARß agonist effects of botanical compounds were screened by an in vitro luciferase reporter gene assay. The PPARß agonist effects of pectolinarigenin (PEC) in bone marrow mesenchymal stromal cells (BMSCs) were validated by Western blotting. RNA-seq transcriptome analyses were conducted to reveal the underlying osteoporosis mechanisms of PEC in BMSCs. The PPARß antagonist (GSK0660) and Wnt signaling inhibitor (XAV969) were used to explore the role of the PPARß and Wnt signaling cascade in the anti-osteoporosis effects of PEC. PEC or the PEG-PLGA nanoparticles of PEC (PEC-NP) were intraperitoneally administrated in both wild-type mice and ovariectomy-induced osteoporosis mice to examine its anti-osteoporotic effects in vivo. RESULTS: PEC, a newly identified naturally occurring PPARß agonist, significantly promotes osteogenic differentiation and up-regulates the osteogenic differentiation-related genes (Runx2, Osterix, and Bmp2) in BMSCs. RNA sequencing and functional gene enrichment analysis suggested that PEC could activate osteogenic-related signaling pathways, including Wnt and PPAR signaling pathways. Further investigations suggested that PEC could enhance Wnt/ß-catenin signaling in a PPARß-dependent manner in BMSCs. Animal tests showed that PEC-NP promoted bone mass and density, increased the bone cell matrix protein, and accelerated bone formation in wild-type mice, while PEC-NP also played a preventive role in ovariectomy-induced osteoporosis mice via maintaining the expression level of bone cell matrix protein, balancing the rate of bone formation, and slowing down bone loss. Additionally, PEC-NP did not cause any organ injury and body weight loss after long-term use (11 weeks). CONCLUSION: PEC significantly promotes bone formation and reduces bone loss in both BMSCs and ovariectomy-induced osteoporosis mice via enhancing the Wnt signaling cascade in a PPARß-dependent manner, providing a new alternative therapy for preventing estrogen deficiency-induced osteoporotic diseases.

Biodesulfurization of organosulfur compounds by a trehalose biosurfactant producing Gordonia sp. isolated from crude oil contaminated soil.

Certain factors hinder the commercialization of biodesulfurization process, including low substrate-specificity of the currently reported desulfurizing bacteria and restricted mass transfer of organic-sulfur compounds in biphasic systems. These obstacles must be addressed to clean organic-sulfur rich petro-fuels that pose serious environmental and health challenges. In current study, a dibenzothiophene desulfurizing strain, Gordonia rubripertincta W3S5 (source: oil contaminated soil) was systematically evaluated for its potential to remove sulfur from individual compounds and mixture of organic-sulfur compounds. Metabolic and genetic analyses confirmed that strain W3S5 desulfurized dibenzothiophene to 2-hydroxybiphenyl, suggesting that it follows the sulfur specific 4 S pathway. Furthermore, this strain demonstrated the ability to produce trehalose biosurfactants (with an EI24 of 53%) in the presence of dibenzothiophene, as confirmed by TLC and FTIR analyses. Various genome annotation tools, such as ClassicRAST, BlastKOALA, BV-BRC, and NCBI-PGAP, predicted the presence of otsA, otsB, treY, treZ, treP, and Trehalose-monomycolate lipid synthesis genes in the genomic pool of strain W3S5, confirming the existence of the OtsAB, TreYZ, and TreP pathways. Overall, these results underscore the potential of strain W3S5 as a valuable candidate for enhancing desulfurization efficiency and addressing the mass transfer challenges essential for achieving a scaled-up scenario.

π Bridge Engineering-Boosted Dual Enhancement of Type-I Photodynamic and Photothermal Performance for Mitochondria-Targeting Multimodal Phototheranostics of Tumor.

Designing mitochondria-targeting phototheranostic agents (PTAs), which can simultaneously possess exceptional and balanced type-I photodynamic therapy (PDT) and photothermal therapy (PTT) performance, still remains challenging. Herein, benzene, furan, and thiophene were utilized as π bridges to develop multifunctional PTAs. STB with thiophene as a π bridge, in particular, benefiting from stronger donor-accepter (D-A) interactions, reduced the singlet-triplet energy gap (ΔES1-T1), allowed more free intramolecular rotation, and exhibited outstanding near-infrared (NIR) emission, effective type-I reactive oxygen species (ROS) generation, and relatively high photothermal conversion efficiency (PCE) of 51.9%. In vitro and in vivo experiments demonstrated that positive-charged STB not only can actively target the mitochondria of tumor cells but also displayed strong antitumor effects and excellent in vivo imaging ability. This work subtly established a win-win strategy by π bridge engineering, breaking the barrier of making a balance between ROS generation and photothermal conversion, boosting a dual enhancement of PDT and PTT performance, and stimulating the development of multimodal imaging-guided precise cancer phototherapy.

Fingerprint characteristics of refined oils and their traceability in the groundwater environment.

Chemical fingerprinting is essential for identifying the presence and responding to oil spills that frequently contaminate the groundwater environment of refineries. In this study, crude oil and oil products from the atmospheric and vacuum distillation units of a refinery were analyzed by gas chromatography-mass spectrometry (GC-MS) to evaluate their chemical variability before and after refinery. A series of experiments involving evaporation and soil column penetration were conducted to simulate refined oil spilling into groundwater and determine appropriate characteristic ratios (CRs) for principal component analysis (PCA) for oil source identification. The simulated study demonstrated that all products had bell-shaped n-alkane distributions, with dominant peaks that remained unchanged or shifted towards longer chain lengths compared to the source oil. Similarly, naphthalene and dibenzothiophene series remained the main PAH components like the source oil. Ten relatively stable CRs were selected for PCA to identify different oil products through the simulated experiments. The chosen CRs were then utilized to identify the sources for two groundwater oil spills recently occurred, one that occurred in an oil depot area, and another near a continuous catalytic reforming unit in a refinery. This study showed that the components with long-chain n-alkanes (n ≥ C18), pristane, phytane, and phenanthrene and dibenzothiophene series PAHs played an important role in the identification of refined oil products spilling into the groundwater environment. The selected CRs provide an effective tool for rapid and accurate identification of oil spills, especially for newly occurring spills in the groundwater environment, which can aid in developing appropriate response strategies.

Isolation of compounds from the roots of Ambrosia artemisiifolia and their effects on human cancer cell lines.

Common ragweed (Ambrosia artemisiifolia L.) is an invasive plant in Europe with spreading use in the contemporary folk medicine. The chemical composition of the above-ground parts is extensively studied, however, the metabolites of the roots are less discovered. By multiple chromatographic purification of the root extracts, we isolated thiophene A (1), n-dodecene (2), taraxerol-3-O-acetate (3), α-linoleic acid (4), (+)-pinoresinol (5), and thiophene E (7,10-epithio-7,9-tridecadiene-3,5,11-triyne-1,2-diol) (6). The 1H NMR data published earlier for 1 were supplemented together with the assignment of 13C NMR data. Thiophene E (6), which is reported for the first time from this species, exerted cytotoxic and antiproliferative effects on A-431 epidermoid skin cancer cells, whereas taraxerol-3-O-acetate (3) and α-linoleic acid (4) had slight antiproliferative effect on gynecological cancer cell lines. Thiophene E (6) and taraxerol-3-O-acetate (3) displayed antiproliferative and cytotoxic effects on MRC-5 fibroblast cells. Thiophene E (6) exerted weak antibacterial activity (MIC 25 µg/mL) on MRSA ATCC 43300, on Staphylococcus aureus ATCC 25923, Escherichia coli AG100 and E. coli ATCC 25922 both thiophenes were inactive. Although the isolated compounds exerted no remarkable cytotoxic or antiproliferative activities, the effects on MRC-5 fibroblast cells highlight the necessity of further studies to support the safety of ragweed root.

Bio-catalytic degradation of dibenzothiophene (DBT) in petroleum distillate (diesel) by Pseudomonas spp.

Biodesulfurization (BDS) was employed in this study to degrade dibenzothiophene (DBT) which accounts for 70% of the sulfur compounds in diesel using a synthetic and typical South African diesel in the aqueous and biphasic medium. Two Pseudomonas sp. bacteria namely Pseudomonas aeruginosa and Pseudomonas putida were used as biocatalysts. The desulfurization pathways of DBT by the two bacteria were determined by gas chromatography (GC)/mass spectrometry (MS) and High-Performance Liquid Chromatography (HPLC). Both organisms were found to produce 2-hydroxy biphenyl, the desulfurized product of DBT. Results showed BDS performance of 67.53% and 50.02%, by Pseudomonas aeruginosa and Pseudomonas putida, respectively for 500 ppm initial DBT concentration. In order to study the desulfurization of diesel oils obtained from an oil refinery, resting cells studies by Pseudomonas aeruginosa were carried out which showed a decrease of about 30% and 70.54% DBT removal for 5200 ppm in hydrodesulfurization (HDS) feed diesel and 120 ppm in HDS outlet diesel, respectively. Pseudomonas aeruginosa and Pseudomonas putida selectively degraded DBT to form 2-HBP. Application of these bacteria for the desulfurization of diesel showed promising potential for decreasing the sulfur content of South African diesel oil.

Genetic and functional characterization of multiple thermophilic organosulfur-removal systems reveals desulfurization potentials for waste residue oil cleaning.

Heavy oil and petroleum refining residues usually contain high concentrations of recalcitrant hazardous organosulfur compounds, causing long-term serious global environmental pollution during leakage and combustion. Research conducted here identified a unique thermophilic bacterium Parageobacillus thermoglucosidasius W-36 with the notable ability of waste residue oil desulfurization, utilization and tolerance of multiplex hazardous organosulfur pollutants. Genome information mining revealed multiple desulfurization systems in three organosulfur-utilizing gene clusters. Enzymatic characterization, phylogenetic relationships, transcriptional performance and structural prediction indicated four novel key monooxygenases for diverse organosulfur removal. Importantly, all monooxygenases shared obvious commonalities in the predicted tertiary structure backbone and catalytic characteristics of C-S bond cleavage, implying the potential of genetic engineering for broad-spectrum hazardous organosulfur removal. Therefore, this work demonstrated the important application potential of thermophilic bacteria as a promising alternative biodesulfurization way for waste residue oil cleaning.

Strontium Ranelate and Strontium Chloride Supplementation Influence on Bone Microarchitecture and Bone Turnover Markers-A Preliminary Study.

Despite strontium ranelate use in osteoporosis management being one of the promising concepts in disease treatment, there is no clear evidence that strontium organic compounds are more effective than inorganic ones. The aim of this study was to compare strontium chlorate and strontium ranelate influence on the mice bone microarchitecture. We investigated whether strontium chlorate (7.532 mmol/L) and strontium ranelate (7.78 mmol/L) solutions fed to healthy SWISS growing mice (n = 42) had an influence on the percent of bone volume (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N), and separation between each trabecula (Tb.Sp) in the chosen ROI (region of interest) in the distal metaphysis of the left femurs. The cortical bone surface was examined close to the ROI proximal scan. There was an increase in each examined parameter compared with the control group. There were no statistical differences between strontium ranelate and strontium chlorate parameters. Our study indicates that organic and inorganic strontium compounds similarly affect the bone microarchitecture and strength.

Analysis of the multi-physiological and functional mechanism of wheat alkylresorcinols based on reverse molecular docking and network pharmacology.

Alkylresorcinols (ARs) are phenolic lipids present in the bran part of whole grain wheat and rye, which possess antioxidant, anti-inflammatory, anti-cancer and anti-tumor properties. The physiological activities of ARs have been proven to be diverse; however, the specific molecular mechanisms are still unclear. In this study, reverse virtual screening and network pharmacology were used to explore the potential molecular mechanisms of the physiological function of ARs and their endogenous metabolites. The Metascape database was used for GO enrichment and KEGG pathway analysis. Furthermore, molecular docking was used to investigate the interactions between active compounds and potential targets. The results showed that the bioavailability of most ARs and their endogenous metabolites was 0.55 and 0.56, while the bioavailability of certain endogenous metabolites was only 0.11. Multiplex analysis was used to screen 73 important targets and 4 core targets (namely, HSP90AA1, EP300, HSP90AB1 and ERBB2) out of the 163 initial targets. The important targets involved in the key KEGG pathway were pathways in cancer (hsa05200), lipid and atherosclerosis (hsa05417), Th17 cell differentiation (hsa04659), chemical carcinogenesis-receptor activation (hsa05207), and prostate cancer (hsa05215). The compounds involved in the core targets were AR-C21, AR-C19, AR-C17, 3,5-DHPHTA-S, 3,5-DHPHTA-G, 3,5-DHPPTA, 3,5-DHPPTA-S, 3,5-DHPPTA-G, 3,5-DHPPTA-Gly and 3,5-DHPPA-G. The interaction force between them was mainly related to hydrogen bonds and van der Waals. Overall, the physiological activities of ARs are not only related to their multiple targets, but may also be related to the synergistic effect of their endogenous metabolites.

Enzymatic Biotransformation of Gypenoside XLIX into Gylongiposide I and Their Antiviral Roles against Enterovirus 71 In Vitro.

Biotransformation of specific saponins in the valuable medical plants to increase their bioavailability and pharmaceutical activities has attracted more and more attention. A gene encoding a thermophilic glycoside hydrolase from Fervidobaterium pennivorans DSM9078 was cloned and expressed in Escherichia coli. The purified recombinant enzyme, exhibiting endoglucanase cellulase activity, was used to transform gypenoside XLIX into gylongiposide I via highly selective and efficient hydrolysis of the glucose moiety linked to the C21 position in gypenoside XLIX. Under the optimal reaction conditions for large scale production of gylongiposide I, 35 g gypenoside XLIX was transformed by using 20 g crude enzyme at pH 6.0 and 80 °C for 4 h with a molar yield of 100%. Finally, 11.51 g of gylongiposide I was purified using a silica gel column with 91.84% chromatographic purity. Furthermore, inhibitory activities of gypenoside XLIX and gylongiposide I against Enterovirus 71 (EV71) were investigated. Importantly, the EC50 of gypenoside XLIX and gylongiposide I calculated from viral titers in supernatants was 3.53 µM and 1.53 µM, respectively. Moreover, the transformed product gylongiposide I has better anti-EV71 activity than the glycosylated precursor. In conclusion, this enzymatic method would be useful in the large-scale production of gylongiposide I, which would be a novel potent anti-EV71 candidate.

Efficient model photosensitizers based on metallocenyl complexes with thiophene-N = N-pyrimidine as π-conjugated bridge and cyanoacrylate as an anchoring group: a density functional theory study.

Eight push-pull systems involving containing four transition metals (iron, ruthenium, cobalt, and nickel), metallocenes as donor groups, cyanoacrylate as electron attractor group, and thiophene-N = N- pyrimidine derivatives as π-conjugated bridges were designed and studied using DFT and TD-DFT methods involving B3LYP and CAM-B3LYP functionals combined with the cc-pVDZ/LANL2DZ basis sets. The main purpose of this work is to determine the effect of metallocene in improving the photosensitization property of such chromophores. This was done by calculating their light-harvesting efficiency LHE as well as other properties employed for DSSC application. The considered dyes were first studied in the gas phase, then in the presence of TiO2 nanoparticles representing the semi-conductor, and finally in the presence of a specific implicit solvent. The presence of iron as metal involved in the metallocene group supplemented by extending the π-conjugated bridge by a cyanovinyl spacer was demonstrated so as to give the most optimal response taking into account the lower cost and toxicity as well as the friendliness to the environment of iron as metal.

Synthesis of Thiophene/Furan-Artemisinin Hybrid Molecules.

Natural products with semi-synthetic molecules displays higher biological activities, and creates new biological properties for the treatment of diseases. Although, natural products like artemisinin have been used as a traditional medicine over thousands of years, structure and biological properties of many natural products were investigated in the 20th century. Design and synthesis of new biologically active compounds including natural products have very critical roles to find novel drug candidates. Herein, novel thiophene/furan bridge artemisinin derivatives were synthesized by starting from artemisinin. Firstly, benzothiophene derivatives are synthesized, then Steglich esterification reactions give the new artemisinin hybrid molecules with moderate to high yields.

Nano selenium repairs the fruit growth and flavor quality of tomato under the stress of penthiopyrad.

This study explored the repair effect of Selenium nanoparticles (Se-NPs) on tomato under the stress of Penthiopyrad (Pen), and expected to select out the optimal concentration and the application time of Se-NPs, to maximize the repair effect without causing phytotoxicity. The results showed that Pen induced severe oxidative stress on tomato and inhibited the growth and flavor quality of fruit. Compared with the control, the application of 1 mg/L Se-NPs at the immature green stage significantly improved the antioxidant capacity of tomato to reduce the MDA content. Besides, the plant hormones were synthesized normally, the contents of soluble sugars, volatile compounds and nutrients were increased, and the contents of organic acids were decreased in the 1 mg/L Se-NPs + Pen treatment group, which finally repaired the fruit flavor and quality. Therefore, the application of 1 mg/L Se-NPs and at the immature green stage represented a promising strategy for repairing the inhibitory effect of Pen on tomato fruit growth and flavor quality.

Identification of thiophene-benzenesulfonamide derivatives for the treatment of multidrug-resistant tuberculosis.

A series of thiophene-benzenesulfonamide derivatives was designed and synthesized by exploring the structure-activity relationship of lead compounds 2,3-disubstituted thiophenes 25a and 297F as antituberculosis agents, which displayed potent antimycobacterial activity against drug-susceptible and clinically isolated drug-resistant tuberculosis. In particular, compound 17b, which had improved activity (minimum inhibitory concentration of 0.023 µg/mL) compared with the lead compounds, displayed good intracellular antimycobacterial activity in macrophages with a reduction of 1.29 log10 CFU. A druggability evaluation indicated that compound 17b had favorable hepatocyte stability, low cytotoxicity, and low hERG channel inhibition. Moreover, compound 17b exhibited modest in vivo efficacy in an acute mouse model of tuberculosis. In addition, the molecular docking study elucidated the binding mode of compound 17b in the active site of DprE1. Therefore, compound 17b may be a promising antituberculosis lead for further research.

Optimization of fermentation for γ-aminobutyric acid (GABA) production by yeast Kluyveromyces marxianus C21 in okara (soybean residue).

γ-Aminobutyric acid (GABA) is a non-protein amino acid with a variety of physiological functions. Recently, yeast Kluyveromyces marxianus strains involved in the catabolism and anabolism of GABA can be used as a microbial platform for GABA production. Okara, rich in nutrients, can be used as a low-cost fermentation substrate for the production of functional materials. This study first proved the advantages of the okara medium to produce GABA by K. marxianus C21 when L-glutamate (L-Glu) or monosodium glutamate (MSG) is the substrate. The highest production of GABA was obtained with 4.31 g/L at optimization condition of culture temperature 35 °C, fermentation time 60 h, and initial pH 4.0. Furthermore, adding peptone significantly increased the GABA production while glucose and vitamin B6 had no positive impact on GABA production. This research provided a powerful new strategy of GABA production by K. marxianus C21 fermentation and is expected to be widely utilized in the functional foods industry to increase GABA content for consumers as a daily supplement as suggested.

Reasonable design of NIR AIEgens for fluorescence imaging and effective photothermal/photodynamic cancer therapy.

The development of a multifunctional single molecule phototherapeutic agent with excellent fluorescence imaging, photothermal therapy and photodynamic therapy at the same time is still a challenging task, which mainly arises from the low absorbance of the molecule, and the complexity of energy dissipation and molecular design. Herein, four donor-acceptor (D-A) compounds were synthesized by linking triphenylamine (TPA), thiophene/thieno[3,2-b]thiophene and different cyano acceptor structures. In this design, we propose a molecular design strategy to redshift absorption and increase the molar extinction coefficient (ε) by enhancing electron-withdrawing acceptors and enlarging the π-conjugation plane unit. Due to the twisted structure of TPA, these compounds exhibit aggregation-induced emission (AIE) characteristics. Notably, these AIEgens have long emission wavelengths, excellent photostability, biocompatibility, photothermal stability and singlet oxygen (1O2) generation performance. Among them, the photothermal conversion efficiency of a compound (named TCF-SS-TPA NPs) can reach 84.5%. Cellular internalization and therapy showed that TCF-SS-TPA NPs have good biocompatibility, excellent cell bioimaging and cancer phototherapy capabilities in vitro. This study will stimulate the molecular design of multifunctional phototherapeutics to realize effective synergistic cancer therapy.

Synthesis and Evaluation of Structurally Diverse C-2-Substituted Thienopyrimidine-Based Inhibitors of the Human Geranylgeranyl Pyrophosphate Synthase.

Novel analogues of C-2-substituted thienopyrimidine-based bisphosphonates (C2-ThP-BPs) are described that are potent inhibitors of the human geranylgeranyl pyrophosphate synthase (hGGPPS). Members of this class of compounds induce target-selective apoptosis of multiple myeloma (MM) cells and exhibit antimyeloma activity in vivo. A key structural element of these inhibitors is a linker moiety that connects their (((2-phenylthieno[2,3-d]pyrimidin-4-yl)amino)methylene)bisphosphonic acid core to various side chains. The structural diversity of this linker moiety, as well as the side chains attached to it, was investigated and found to significantly impact the toxicity of these compounds in MM cells. The most potent inhibitor identified was evaluated in mouse and rat for liver toxicity and systemic exposure, respectively, providing further optimism for the potential value of such compounds as human therapeutics.

Guidelines for surfactant selection to treat petroleum hydrocarbon-contaminated soils.

The present study determined the most effective surfactants to remediate gasoline and diesel-contaminated soil integrating information from soil texture and soil organic matter. Different ranges for aliphatic and aromatic hydrocarbons (> C6-C8, > C8-C10, > C10-C12, > C12-C16, > C16-C21, and > C21-C35) in gasoline and diesel fuel were analyzed. This type of analysis has been investigated infrequently. Three types of soils (silty clay, silt loam, and loamy sand) and four surfactants (non-ionic: Brij 35 and Tween 80; anionic: SDBS and SDS) were used. The results indicated that the largest hydrocarbon desorption was 56% for silty clay soil (SDS), 59% for silt loam soil (SDBS), and 69% for loamy sand soil (SDS). Soils with large amounts of small particles showed the worst desorption efficiencies. Anionic surfactants removed more hydrocarbons than non-ionic surfactants. It was notable that preferential desorption on different hydrocarbon ranges was observed since aliphatic hydrocarbons and large ranges were the most recalcitrant compounds of gasoline and diesel fuel components. Unlike soil texture, natural organic matter concentration caused minor changes in the hydrocarbon removal rates. Based on these results, this study might be useful as a tool to select the most cost-effective surfactant knowing the soil texture and the size and chemical structure of the hydrocarbons present in a contaminated site.