Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis.

Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for anti-inflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development.

Assessment of heavy metals contamination and human health risk assessment of the commonly consumed medicinal herbs in China.

This study investigates heavy metal contamination of commonly consumed medicinal herbs and human health risks to the Chinese population arising from the consumption of herbs that contain potentially harmful elements. Food safety standards for Chinese residents are becoming stricter, and much work in this field needs to be performed. This study examines Co, Ba, Fe, Cr, Mn, Ni, Zn, As, Cd, Pb, Cu, Be, Sb, and Bi concentrations in four regularly consumed Chinese herb species: Radix Paeoniae Alba (RPA), Radix Angelicae Dahuricae (RAD), Rhizoma Atractylodis Macrocephalae (RAM), and Radix Puerariae (RP). A pollution status examination and evaluation of heavy metals in RPA, RAD, RAM, and RP were performed. The human health risk assessment associated with the intake of potentially harmful elements in herbs was calculated in terms of the estimated daily intake (EDI), the target hazard quotient (THQ), the estimated hazard index (HI), and the lifetime cancer risk (CR). The mean single-factor pollution index (PI) showed that in the RPA, RAD, RAM, and RP samples, approximately 10.0%, 10.0%, 30.0%, and 10.0%, respectively, were polluted by Cd. The present study indicated that the pattern of consumption of the studied herbs in China does not seem to suggest an excessive health hazard associated with any of the toxic elements studied.

The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies.

Streptomyces scabies is the best-characterized plant-pathogenic streptomycete, which is a special species among the large genus Streptomyces. The pathogenicity of S. scabies relies on the production of the secondary metabolite thaxtomin A. Little is known about the molecular mechanisms underlying the regulation of thaxtomin biosynthesis in S. scabies beyond the pathway-specific activator TxtR and the cellulose utilization repressor CebR. The leucine-responsive regulatory protein (Lrp) family modulates secondary metabolism in nonpathogenic streptomycetes. However, the regulatory relationship between the Lrp and pathogenic streptomycetes remains unknown. In this study, we demonstrated that SCAB_Lrp (SCAB_77931) from S. scabies significantly affects thaxtomin biosynthesis, pathogenicity, and morphological development. SCAB_Lrp deletion resulted in a dramatic decline in thaxtomin A production and a low-virulence phenotype of S. scabies. An in-depth dissection of the regulatory mechanism of SCAB_Lrp revealed that it positively regulates the transcription of the thaxtomin biosynthetic gene cluster by directly binding to the promoter of the cluster-situated regulator gene txtR. SCAB_Lrp also controls the morphological development of S. scabies by directly activating the transcription of amfC, whiB, and ssgB. SCAB_Lrp directly controls the transcription of its own gene by binding a specific sequence (5'-GGACAGTCGCCGTGCTACG-3'). Moreover, phenylalanine and methionine have been characterized as SCAB_Lrp effectors by strengthening the binding affinity and complex status between SCAB_Lrp and DNA. Our findings characterize a multifunctional regulatory protein, SCAB_Lrp, that controls secondary metabolism, pathogenicity, and sporulation in S. scabies and provide new insights into the complex regulatory network that modulates thaxtomin phytotoxins in pathogenic Streptomyces.

Multiple responses optimization of antioxidative components extracted from Fenugreek seeds using response surface methodology to identify their chemical compositions.

Fenugreek seeds (Trigonella foenum-graecum L.), one kind of traditional Chinese medicine, are reported to be of great potential as a new alternative in terms of their bioactive components. In our present study, an ultrasonic-assisted method was applied in the extraction of antioxidative components from fenugreek seeds. Four factors: ethanol concentration, liquid-solid ratio, sonication time, and sonication power were selected and multiple responses were studied using the response surface methodology (RSM). The effects of factors along with the correlation between all responses (flavonoids content, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, OH- assay) were studied. The regression model indicated that all four factors are of significant effect on all responses. The model predicted that the ethanol concentration of 72%, solvent-to-material ratio of 35 ml/g, ultrasonic time of 41 min, and 500 W of power would provide a flavonoid yield of 9.10 mg/g, DPPH clearance of 80.33%, and OH- clearance of 24.28%, respectively. The confirmation test showed the closeness of the predicted results with those of experimental values. And AB-8 resin was successfully used to purify the fenuellus hulusi seed extract, and the flavonoid concentration of 78.14% was obtained. Six flavonoids (Swertisin, Puerarin apioside, Jasminoside B, Astragalin, Apigenin-7-O-beta-D-glucoside, and Apiin) were successfully identified by the liquid chromatography-mass spectrometry (LC-MS) analysis.

A rational design of copper-selenium nanoclusters that cures sepsis by consuming endogenous H2S to trigger photothermal therapy and ROS burst.

The treatment of sepsis caused by bacterial infections is still a huge clinical challenge. As sepsis causes high levels of endogenous H2S in vivo, researchers can design nanomedicines to treat sepsis by in situ sulfurization. Here, we designed and synthesized Cu2O-coated non-metallic core-shell selenium nanoparticles. To cure mice sepsis by ROS burst. Our experimental data displayed that the photothermal effect of Se@Cu9S8 produced by the reaction of Se@Cu2O and endogenous H2S is synergistically antibacterial, and Se@Cu2O has the characteristics of low side effects and high biocompatibility. In summary, our research results verified our design, that copper-selenium nanoclusters may be an efficient strategy to cure sepsis by in situ sulfurization of endogenous H2S, triggering ROS eruptions and photothermal therapy.

Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy.

Photothermal therapy as novel strategy to convert near-infrared (NIR) light into heat for treatment cancers has attracted great attention and been widely studied. However, side effects and low efficiency remain the main challenge of precise cancer photothermal therapy. Methods: In this study, we have successfully fabricated and characterized the dual-targeted gold nanoprisms, whereby bare gold nanoprisms (Au NPR) were conjugated to a phenanthroline derivatives-functionalized tetraphenylethene (TPE) and further stabilized with target peptide aptamers via Au-S bonds (Au-Apt-TPE). Then, the remaining nitrogen atoms of the Au-Apt-TPE could effectively chelate with Zn2+ ions (Au-Apt-TPE@Zn) for monitoring early stage apoptotic cells. Results: The as-synthesized Au-Apt-TPE@Zn exhibited good monodispersity, size stability and consistent spectral characteristics. TPE synthesized here showed aggregation-induced emission (AIE) characteristics, and zinc conjunction (TPE@Zn) endowed Au-Apt-TPE@Zn with the cell membrane-targeted ability to selectively recognize the membranes of early stage apoptotic cells but not respond to healthy cells, which provided valuable diagnosis information on therapeutic efficacy. Au-Apt-TPE@Zn achieved specifically nuclear-targeted ability by surface decoration of AS1411 DNA aptamer. Au-Apt-TPE@Zn under NIR irradiation showed effective photothermal therapy against SGC-7901 human gastric carcinoma cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and regulating multiple signal crosstalk. In vivo studies revealed that Au-Apt-TPE@Zn under NIR irradiation showed deep penetration and dual-model imaging application (cancer-targeted fluorescence imaging and light-up photoacoustic imaging). Au-Apt-TPE@Zn under NIR irradiation also displayed strong photothermal therapy against gastric carcinoma xenograft growth in vivo by induction of apoptosis. Importantly, analysis of histopathology, hematotoxicity and immunocytotoxicity indicated that Au-Apt-TPE@Zn had less side effect and high biocompatibility. Conclusions: Our findings validated the design of using Au nanoprism with AIE materials and dual-targeted decoration could be an effective strategy in recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy.

Self-assembled thermal gold nanorod-loaded thermosensitive liposome-encapsulated ganoderic acid for antibacterial and cancer photochemotherapy.

A novel nanoparticle (Au-LTSL-GA.A) uses the thermosensitive liposome (LTSL) to encapsulate ganoderic acid A (GA.A), which successfully transforms the polarity of GA.A and has excellent water solubility. The multifunctional Au-LTSL-GA.A, a self-assembled thermal nanomaterial, was used in antibacterial and anticancer applications in combination with near-infrared (NIR) irradiation. The designed Au-LTSL-GA.A nanoparticle was used as a nano-photosensitizer to achieve synergistic photochemotherapy based on the phototherapy sensitization property of Au nanorods (NRs) and antitumour activity of GA.A. In the antibacterial experiments, the Au-LTSL-GA.A + NIR irradiation had a broad-spectrum antibacterial effect, exhibiting a strong antibacterial activity against drug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) compared with the raw GA.A and LTSL-GA.A. In the anticancer experiments, Au-LTSL-GA.A + NIR irradiation, which combined phototherapy sensitization property of Au NRs with antitumour activity of GA.A, exhibited high anticancer activity against MCF-7 cells. The IC50 value of Au-LTSL-GA.A + NIR irradiation (12.1 ± 1.3 µg/mL) was almost similar to cisplatin in MCF-7 cells. The evaluation of the potential in vivo toxicity of Au-LTSL-GA.A revealed no toxicity in mice. The results of this study suggest that Au-LTSL-GA.A has a wide range of potential industrial and clinical applications, such as in antibacterial treatment and cancer photochemotherapy.

Transformation of apatite phosphorus and non-apatite inorganic phosphorus during incineration of sewage sludge.

The recovery of phosphorus from incinerated sewage sludge ash (SSA) is assumed to be economical. Transformation from non-apatite inorganic phosphorus (NAIP) to apatite phosphorus (AP), which has a higher bioavailability and more extensive industrial applications, was studied at 750-950°C by sewage sludge incineration and model compound incineration with a calcium oxide (CaO) additive. Thermogravimetric differential scanning calorimetry analysis and X-ray diffraction measurements were used to analyze the reactions between NAIP with CaO and crystallized phases in SSA. High temperatures stimulated the volatilization of NAIP instead of AP. Sewage sludge incineration with CaO transformed NAIP into AP, and the percentage of AP from the total phosphorus reached 99% at 950°C. Aluminum phosphate reacted with CaO, forming Ca2P2O7 and Ca3(PO4)2 at 750-950°C. Reactions between iron phosphate and CaO occurred at lower temperatures, forming Ca(PO3)2 before reaching 850°C.

Analysis of volatile compounds from Siraitia grosvenorii by headspace solid-phase microextraction and gas chromatography-quadrupole time-of-flight mass spectrometry.

Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF MS) has been used in the present study to isolate and identify volatile components from Siraitia grosvenorii, a herbaceous perennial vine used as a natural sweetener and medicine. Compared with the static HS extraction and the different SPME fiber coatings, HS-SPME with divinylbenzene/carboxen/polydimethylsiloxane fiber was preferred to extract the target analytes including aldehyde, alcohol, acid, ester and other compounds. In the identification, a multi-dimensional qualitative analysis approach containing library searching, retention index comparison, accurate mass measurement, the second-stage mass spectrum (MS(2) spectrum) and area normalization was utilized. Finally, a total of 46 compounds were identified from S. grosvenorii. Among them, n-hexadecanoic acid, 5-hydroxymethylfurfural, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, (Z, Z)-9,12-octadecadienoic acid and (E, E)-2,4-nonadienal were the main volatile components. The results showed that HS-SPME coupled with GC-QTOF MS is efficient for the extraction of polar volatiles from S. grosvenorii and accurate for the identification of volatile compounds in the complicated matrix.

Heavy metal removal and speciation transformation through the calcination treatment of phosphorus-enriched sewage sludge ash.

On the basis of the heavy metal (Cd, As, Pb, Zn, Cu, Cr, and Ni) control problem during the thermochemical recovery of phosphorus (P) from sewage sludge (SS), P-enriched sewage sludge ash (PSSA) was calcined at 1100°C. The effect of organic chlorinating agent (PVC) and inorganic chlorinating agent (MgCl2) on the fixed rate of P removal and the speciation transformation of heavy metal was studied. The removal of heavy metals Cd, Pb, As, Zn, and Cr exhibited an increasing tendency with the addition of chlorinating agent (PVC). However, an obvious peak under 100gCl/kg of PSSA appeared for Cu, owing to the presence of carbon and hydrogen in PVC. MgCl2 was found to be more effective than PVC in the removal of most heavy metals, such that up to 98.9% of Cu and 97.3% of Zn was effectively removed. Analyses of heavy metal forms showed that Pb and Zn occurred in the residue fraction after calcination. Meanwhile, the residue fraction of Cr, Ni, Cd, and Cu exhibited a decreasing tendency with the increase in the added chlorinating agent (MgCl2). Losses of P from PSSA were around 16.6% without the addition of chlorinating agent, which were greatly reduced to around 7.7% (PVC) and to only 1.7% (MgCl2).

Transformation of phosphorus during drying and roasting of sewage sludge.

Sewage sludge (SS), a by-product of wastewater treatment, consists of highly concentrated organic and inorganic pollutants, including phosphorus (P). In this study, P with different chemical fractions in SS under different drying and roasting temperatures was investigated with the use of appropriate standards, measurements, and testing protocol. The drying and roasting treatment of SS was conducted in a laboratory-scale furnace. Two types of SS samples under different treatment temperatures were analyzed by (31)P NMR spectroscopy. These samples were dried by a vacuum freeze dryer at -50°C and a thermoelectric thermostat drying box at 105°C. Results show that the inorganic P (IP) content increased as the organic P content decreased, and the bio-availability of P increased because IP is a form of phosphorousthat can be directly absorbed by plants. (31)P NMR analysis results indicate the change in P fractions at different temperatures. Non-apatite P was the dominant form of P under low-temperature drying and roasting, whereas apatite P was the major one under high-temperature drying and roasting. Results indicate that temperature affects the transformation of P.