Extracellular vesicles: a rising star for therapeutics and drug delivery.

Extracellular vesicles (EVs) are nano-sized, natural, cell-derived vesicles that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve as natural carriers for therapeutic agents and drugs, and have many advantages over conventional nanocarriers, including their low immunogenicity, good biocompatibility, natural blood-brain barrier penetration, and capacity for gene delivery. This review first introduces the classification of EVs and then discusses several currently popular methods for isolating and purifying EVs, EVs-mediated drug delivery, and the functionalization of EVs as carriers. Thereby, it provides new avenues for the development of EVs-based therapeutic strategies in different fields of medicine. Finally, it highlights some challenges and future perspectives with regard to the clinical application of EVs.

Comparison of Ophiopogon japonicus and Liriope spicata var. prolifera from Different Origins Based on Multi-Component Quantification and Anticancer Activity.

The tuberous root of Ophiopogon japonicus (Thunb.) Ker-Gawl. is a well-known Chinese medicine also called Maidong (MD) in Chinese. It could be divided into "Chuanmaidong" (CMD) and "Zhemaidong" (ZMD), according to the geographic origins. Meanwhile, the root of Liriope spicata (Thunb.) Lour. var. prolifera Y. T. Ma (SMD) is occasionally used as a substitute for MD in the market. In this study, a reliable pressurized liquid extraction and HPLC-DAD-ELSD method was developed for the simultaneous determination of nine chemical components, including four steroidal saponins (ophiopojaponin C, ophiopogonin D, liriopesides B and ophiopogonin D'), four homoisoflavonoids (methylophiopogonone A, methylophiopogonone B, methylophiopogonanone A and methylophiopogonanone B) and one sapogenin (ruscogenin) in CMD, ZMD and SMD. The method was validated in terms of linearity, sensitivity, precision, repeatability and accuracy, and then applied to the real samples from different origins. The results indicated that there were significant differences in the contents of the investigated compounds in CMD, ZMD and SMD. Ruscogenin was not detected in all the samples, and liriopesides B was only found in SMD samples. CMD contained higher ophiopogonin D and ophiopogonin D', while the other compounds were more abundant in ZMD. Moreover, the anticancer effects of the herbal extracts and selected components against A2780 human ovarian cancer cells were also compared. CMD and ZMD showed similar cytotoxic effects, which were stronger than those of SMD. The effects of MD may be due to the significant anticancer potential of ophiopognin D' and homoisoflavonoids. These results suggested that there were great differences in the chemical composition and pharmacological activity among CMD, ZMD and SMD; thus, their origins should be carefully considered in clinical application.

Oil-water partition coefficient preparation and detection in the dihydroartemisinin self-emulsifying drug delivery system.

BACKGROUND: The aim of the present study is to increase the solubility of dihydroartemisinin (DHA) using the self-emulsifying drug delivery system (SEDDS). METHODS: We first conducted solubility test and ternary phase diagram, then, in order to optimize the formulation of the DHA self-emulsifying agent, the design mixture method was selected in the design expert software. Next, optimal prescription validation and preliminary formulation evaluation were conducted. By comparing the oil-water partition coefficient in vitro, the improvement of the in vivo osmotic absorption of DHA via self-emulsification was evaluated. RESULTS: The optimal prescription ratio of oleic acid polyethylene glycol glyceride, polyoxyethylene hydrogenated castor oil, and diethylene glycol monoethyl ether in the DHA self-emulsifying preparation = 0.511:0.2:0.289 (w/w/w), with a drug-loading capacity of 26.3634 mg/g, solubility of 2.5448 mg/ml, and self-emulsification time of 230 s. The solubility self-emulsification was approximately 20.52 × higher in DHA than in the crude drug. The self-emulsification could improve DHA permeability and promoting in vivo DHA absorption. CONCLUSION: The DHA SEDDS could significantly improve DHA solubility and in vivo absorption.

An efficient and cost-effective method for the purification of human basophils.

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

Bioinspired, Ultra-Fast Polymerization of Dopamine under Mild Conditions.

Spontaneous oxidative polymerization of dopamine (DA) is widely exploited as a facile and versatile method for surface modification. However, the reaction is very slow and only occurs in alkaline solutions, which severely limit its applications. Herein it is reported that the reaction can be dramatically accelerated by using Fe2+ as catalyst. While it takes hours and days using conventional method, the Fe2+ -catalyzed reaction finishes almost immediately at pH 7.0. In addition, under the catalysis of Fe2+ , the reaction can occur at a pH down to 4.0. The fast Fe2+ -catalyzed polymerization of DA leads to fast deposition of polydopamine (PDA) coating, thus allowing fast surface modification and textile dyeing. The Fe2+ -catalyzed reaction also allows spatial control over the PDA deposition. The fast, simple, and mild surface modification method developed here will find applications in numerous fields.

Membrane intercalation-enhanced photodynamic inactivation of bacteria by a metallacycle and TAT-decorated virus coat protein.

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

Conjugating Peptides onto 1D Rodlike Bionanoparticles for Enhanced Activity against Gram-Negative Bacteria.

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

[Research Progress in Regulation of Allergic Diseases by Short-Chain Fatty Acids].

Gut microbiota-derived metabolites play vital roles in the regulation of host-gut microbiota mutualism, gut homeostasis and the pathogenesis of multiple human diseases. Fermentation of indigestible dietary fibers by gut microbiota produces a variety of short-chain fatty acids (SCFAs) consisting mainly of acetate, propionate and butyrate. Despite high concentrations of SCFAs in the gut, it has been reported in a large number of studies that SCFAs are involved in the onset and development of multiple diseases, including colitis, diabetes mellitus, hepatic steatosis, and obesity. Recent studies including our work found that SCFAs regulates allergic immune reactions and the pathogenesis of allergic diseases via their action on allergic effector immune cells, including T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), eosinophils, mast cells and basophils. Herein, we reviewed the association of SCFAs with human allergic diseases, their role in regulating the animal model of allergic diseases and the effects of different SCFAs in regulating the functions of allergic effectors cells and the underlying mechanisms, aiming to provide research clues for in-depth investigation in the role played by SCFAs in regulating various allergic diseases.

Induction of the apoptosis, degranulation and IL-13 production of human basophils by butyrate and propionate via suppression of histone deacetylation.

Allergic diseases are caused by dysregulated Th2 immune responses involving multiple effector cells including basophils. Short chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, exert immunomodulatory functions via activation of its receptors GPR41 and GPR43, and inhibition of the histone deacetylases (HDACs) activity. In allergic diseases, SCFAs suppress the activity of mast cells, eosinophils and type 2 innate lymphoid cells (ILC2) but enhance the function of Th2 cells. Here, we aimed to elucidate the function of SCFAs on human basophils. Human basophils were purified from healthy donors by flow cytometric sorting. The surface proteins, apoptosis and degranulation of basophils were analyzed by flow cytometric analysis. The mRNA expression was assayed using real-time PCR. Interleukin 4 (IL-4) and IL-13 were measured by ELISA. Histone acetylation was examined by western blot. GPR41 was expressed by basophils and was enhanced by IL-3. Acetate induced intracellular calcium influx in basophils which was suppressed by blocking GPR41. Propionate and butyrate, but not acetate, induced the expression of CD69 and IL-13. In addition, propionate and butyrate enhanced IgE-mediated basophil degranulation but inhibited basophil survival and IL-4 secretion. Propionate and butyrate induced histone acetylation of basophils and suppression of HDACs activity mimicked the effects of propionate and butyrate on human basophils. Our findings demonstrate that propionate and butyrate may play a complex role in regulating basophil apoptosis, activation and degranulation via inhibiting HDACs activity. The in vivo effects of SCFAs on the regulation of basophil-associated allergic diseases need to be further explored.

Interleukin 3-induced GITR promotes the activation of human basophils.

Human basophils regulate allergic reactions by secreting histamine, interleukin 4 (IL-4) and IL-13 through key surface receptors FcεRI as well as IL-3R, which are constitutively expressed on basophils. IL-3/IL-3R signaling axis plays key roles in regulating the development and activation of basophils. We and others have shown that IL-3-induced surface receptors e.g. ST2, IL-17RB and IL-2 receptors regulate the biology of basophils. However, the expression and function of IL-3-induced surface proteins on human basophils remain to be elucidated. We in this study aimed to identify new basophil activation regulators by transcriptomic analysis of IL-3-stimulated basophils. Gene expression microarray analysis of IL-3-treated basophils revealed 2050 differentially expressed genes, of which 323 genes encoded surface proteins including GITR. We identified that GITR was preferentially induced by IL-3 rather than anti-IgE, IL-33, fMLP and C5a. IL-3-induced GITR was suppressed by inhibitors targeting JAK2, PI3K and MEK1/2. Stimulation of IL-3-treated basophils by GITR enhanced the expression of IL-4 and IL-13. Moreover, IgE-mediated degranulation was enhanced by GITRL in the presence of IL-3. This transcriptomic analysis of IL-3-activated basophils helps to identify novel activation regulator. IL-3-induced GITR promoted the activation of basophils, adding new evidence supporting GITR as an important player in Th2-associated immune responses.

Differentiating atypical hemangiomas and vertebral metastases: a field-of-view (FOV) and FOCUS intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) study.

PURPOSE: Some atypical vertebral hemangiomas (VHs) may mimic metastases on routine MRI and can result in misdiagnosis and ultimately to additional imaging, biopsy and unnecessary costs. The purpose of this study is to assess the utility of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) on account of field-of-view optimized and constrained undistorted single shot (FOCUS) in distinguishing atypical VHs and vertebral metastases. METHODS: A total of 25 patients with vertebral metastases and 25 patients with atypical VHs were confirmed by clinical follow-up or pathology. IVIM-DWI imaging was performed at different b values (0, 30, 50, 100, 150, 200, 400, 600, 800, 1000 mm2/s). IVIM parameters [the true diffusion coefficient (D), pseudodiffusion coefficient (D*), standard apparent diffusion coefficient (ADC), and perfusion fraction (f)] were calculated and compared between two groups by using Student's t test. A receiver operating characteristic analysis was performed. RESULTS: Quantitative analysis of standard ADC and D parameters showed significantly lower values in vertebral metastases when compared to atypical hemangiomas [ADC value: (0.70 ± 0.12) × 10-3 mm2/s vs (1.14 ± 0.28) × 10-3 mm2/s; D value: (0.47 ± 0.07) × 10-3 mm2/s vs (0.76 ± 0.14) × 10-3 mm2/s, all P < 0.01]. The sensitivity and specificity of D value were 93.8% and 92.3%, respectively. CONCLUSION: The standard ADC value and D value may be used as an indicator to distinguish vertebral metastases from atypical VHs. FOCUS IVIM-derived parameters provide potential value in the quantitatively differentiating vertebral metastases from vertebral atypical hemangiomas.

Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology.

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.

Clinical application and diagnostic value of noninvasive spinal angiography in spinal vascular malformations.

OBJECTIVE: The purpose of this study was to explore the value of computed tomographic (CT) spinal angiography with 256-slice CT and fast dynamic contrast-enhanced 3-dimensional magnetic resonance angiography (MRA) at 3.0 T in the diagnosis of spinal vascular malformations. METHODS: Seventeen patients who presented with suspected spinal vascular diseases by initial magnetic resonance and clinical findings all underwent CT spinal angiography. Among these, 10 patients underwent MRA, 15 patients underwent digital subtraction angiography (DSA) within 3 to 5 days, and 8 patients finally underwent surgical treatment. RESULTS: Computed tomographic angiography examination clearly showed the abnormal vascular lesions in 16 of the 17 patients, including 7 patients with the diagnosis of spinal dural arteriovenous fistula, 7 patients with perimedullary arteriovenous fistula, and 2 patients with spinal arteriovenous malformations. The results were consistent with the diagnosis of DSA or surgery. One patient was poorly diagnosed. The fistulas could be seen in 12 patients; feeding arteries were correctly displayed in 12 patients. The fistulas and feeding arteries were accurately shown in 7 of 10 patients by MRA; DSA results were also negative in the other 3 patients. CONCLUSIONS: Spinal angiography with 256-slice CT and contrast-enhanced MRA at 3.0 T can clearly show the extent of spinal vascular malformations, feeding arteries, and fistulas. They are safe, noninvasive, as well as rapid and can shorten the time of DSA diagnosis and treatment.

Increasing impacts of China's oil and gas demands on global CH4 emissions.

The energy sector stands out as a main contributor to increasing global methane (CH4) emissions. Given China's heavy dependence on energy imports, a closer examination of its oil and gas-related CH4 emissions becomes imperative. This study conducts an in-depth analysis of China's contribution to global CH4 emissions stemming from its consumption of crude oil and natural gas since 2000. The results indicate that CH4 emissions from crude oil and natural gas imports rose from 614 Gg in 2000 to 7692 Gg in 2019. When considering domestic production, the demand-induced CH4 emissions in 2019 increased to approximately 10754 Gg (equivalent to 320 Mt CO2-eq and 887 Mt CO2-eq based on global warming potential (GWP) values at the 100-year and 20-year time period), of which 72 % were related to crude oil and natural gas imports. The primary contributor to this increase in CH4 emissions was the expansion of the trade scale. The growth trend of crude oil imports-induced CH4 emissions was also positively influenced by emission intensity and trade structure, but these two drivers had a negative impact on the growth of natural gas imports-induced CH4 emissions. The virtual transfer of CH4 emissions via international oil and gas trade requires urgent policy attention. In collaboration with its trading partners, China should take aggressive actions to achieve meaningful mitigation in CH4 emissions associated with the oil and gas trade.

Association of dietary intake of B vitamins with glaucoma.

This cross-sectional study investigated the association between glaucoma and B vitamin dietary intake. A total of 5025 enrolled individuals participated in self-reported glaucoma questionnaire and 3264 participated in International Society Geographical and Epidemiological Ophthalmology (ISGEO) criteria. In self-reported glaucoma, the risk of having self-reported glaucoma was lower in the third quartile of vitamin B1 intake (odds ratio [odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40-0.97), and P trend (P trend = 0.004) for vitamin B12 was significant; in males, the third quartile of vitamin B1 intake (OR 0.44, 95% CI 0.24-0.83) and the fourth quartile of vitamin B2 intake (OR 0.39, 95% CI 0.17-0.89) were associated with a lower risk. In glaucoma based on ISGEO criteria, the increase of niacin intake (OR 0.94, 95% CI 0.89-0.99) was negatively associated with the odds of self-reported glaucoma. After sex-stratified analysis, the third quartile of vitamin B6 intake (OR 0.21, 95% CI 0.08-0.60) in males were associated with reduced odds of glaucoma. The restricted cubic spline analysis revealed a nonlinear association of vitamin B2 (p for nonlinearity = 0.04) and B9 (p for nonlinearity = 0.024) intake with glaucoma diagnosed by ISGEO criteria in females.

Promotion of 14-3-3ζ/Heme Oxygenase-1 Axis on Endotoxin-Induced Uveitis and Microglia Ferroptosis in Mice.

PURPOSE: Uveitis is a common, sight-threatening inflammatory ocular disease and is the main cause of blindness, which is caused by autoimmune response, infection, and injury. The contribution of 14-3-3ζ in uveitis remains obscure. This study aims to investigate the role of 14-3-3ζ in regulating ferroptosis in retinal inflammation and its contribution to uveitis. METHODS: A lipopolysaccharide (LPS)-induced uveitis mouse model and BV-2 cell line were used to examine the effect of LPS stimulation on the expression of 14-3-3ζ and ferroptosis in microglia. The expression of heme oxygenase-1 (HO-1) was also analyzed to understand its role in promoting microglial ferroptosis. RESULTS: We found that LPS stimulation increased the expression of 14-3-3ζ and promoted ferroptosis in microglia. Additionally, 14-3-3ζ was found to promote microglial ferroptosis by stabilizing the expression of HO-1. These findings suggest that the 14-3-3ζ/HO-1 axis plays a crucial role in promoting microglial ferroptosis in retinal inflammation. CONCLUSION: The study provides valuable insights into the mechanisms underlying uveitis and highlights the potential of the 14-3-3ζ/HO-1 axis as a therapeutic target for the disease. Further research in this area could lead to the development of preventive and therapeutic strategies for uveitis.

Liquid crystalline composite hydrogels with large pH-triggered anisotropic swelling for embolotherapy.

Inspired by the anisotropic structure of biological tissues, anisotropic hydrogels have been developed using various nanofillers, however, it remains a big challenge to synthesize hydrogels with large swelling anisotropy. Herein a single molecule filler, α-helical polypeptide, instead of nanoscale fillers, was used to synthesize anisotropic hydrogels. First nematic liquid crystal of poly(γ-benzyl l-glutamate) (PBLG) was prepared by shearing and stabilized by embedding in a crosslinked polymer matrix. The resulting PBLG composite gels were then converted to poly(L-glutamic acid) (PLGA) composite gels by debenzylation. The rigid rod-like structure of α-helical PBLG chains makes them easy to be orientated. The pH-sensitivity of PLGA makes the resulting composite gels pH-sensitive without the need to couple with a stimuli-responsive hydrogel matrix. In response to pH change PLGA composite gels swell anisotropically with a much larger swelling degree in the radial direction than in the axial direction. The swelling anisotropy (3.43) is much higher than most anisotropic hydrogels, particularly the stimuli-responsive ones reported previously. The composite gel also exhibits anisotropic mechanical properties with a larger Young's modulus in the axial direction than that in the radial direction. Preliminary test demonstrated that the composite gels have potential in embolotherapy thanks to its large pH-triggered anisotropic swelling. STATEMENT OF SIGNIFICANCE: Anisotropic hydrogels have important biomedical applications. Introduction of oriented nanofillers has been demonstrated a popular and versatile method for their synthesis, however, it remains a big challenge to achieve large swelling anisotropy. Herein a single molecule filler, α-helical polypeptide, instead of nanoscale fillers, was used to synthesize anisotropic hydrogels. This filler can be easily oriented by shearing. More importantly, as single molecule filler, it can constrain the swelling of hydrogel matrix more effectively. Using this filler, a pH-sensitive hydrogel with large swelling anisotropy (3.43) was successfully synthesized. Thanks to its large pH-triggered anisotropic swelling the hydrogel was successfully used as embolic agent to occlude vessels.

Comparison of different phosphate species adsorption by ferric and alum water treatment residuals.

As safe byproducts of drinking water treatment processes, ferric and alum water treatment residuals (FARs) have the potential to be new phosphate (P) immobilization materials. In this study, batch experiments were conducted to investigate and compare the adsorption characteristics of three P species by FARs. The results showed that the kinetic processes of different P species' adsorption by FARs could be described by a pseudo second-order model. The ranking list of the initial adsorption rates with respect to different phosphates was pyrophosphate, phytate, orthophosphate, hexametaphosphate and glycerophosphate. Of the six models considered, the two-site Langmuir model most effectively described the adsorption characteristics of the various P species. Upon fitting the results, the maximum adsorption capacities were determined to be 40.24 mg/g for phytate, 18.04 mg/g for pyrophosphate, 17.14 mg/g for orthophosphate, 15.86 mg/g for hexametaphosphate and 10.81 mg/g for glycerophosphate. In addition, the adsorption processes of the different P species were spontaneous endothermic processes and were favored at lower pH values. The pH dependency was found to be especially true for orthophosphate, where the adsorption capacity decreased by 1.22 mg/g with an increase in pH from 5 to 9. Fractionation of the adsorbed P species from the FARs demonstrated that Al-P and Fe-P were the dominating forms, constituting approximately 80%-90% of the total P fractions, which indicated that the adsorbed P species had a low leaching risk and could stably exist in the FARs. Therefore, the FARs could be effective in controlling pollution in water caused by different P species.

Rehabilitation and improvement of Guilin urban water environment: function-oriented management.

Economic development and population growth have deeply damaged the urban water environment of Guilin City, China. Main problems involved structural damage and functional deterioration of the urban waters. An integrated technical scheme was developed to rehabilitate the urban water environment and to enhance the waters' functions during 1998-2008. Improvement of waters' functions included water system reconstruction, water pollution control, water safety assurance, and aquatic ecological restoration. The water system was reconstructed to connect different waters and clean water supplies to the lakes. Moreover, water pollution was controlled to improve water quality by endogenous pollutant elimination and extraneous pollutant interception. In addition, ecological measures put in place serve to enhance water system functions and better benefit both nature and humans. The project has brought about sound ecological, economic and social benefits in Guilin City, which can potentially be extended to similar cities.

Allicin ameliorates imiquimod-induced psoriasis-like skin inflammation via disturbing the interaction of keratinocytes with IL-17A.

BACKGROUND AND PURPOSE: Psoriasis is an inflammatory skin disease of chronic recurrence mediated by the interaction between IL-17 and keratinocytes, which sustains a vicious circle of inflammation. Safe and effective natural medicine is a potential strategy for the clinical treatment of psoriasis. Given its prominent anti-proliferative and anti-inflammatory properties, we investigated the actions of allicin in improving psoriasis. EXPERIMENTAL APPROACH: Pharmacodynamic studies were carried out in mice after topical administration of allicin against psoriasis-like lesions induced by imiquimod. Skin sensitization tests were evaluated on guinea pigs. Toxicological studies and skin irritation tests were assessed by consecutive topical allicin alone on the skin of rabbits. RNA-seq probed transcriptomic changes following allicin. Western blot explored the actions of allicin on the interaction between IL-17A and keratinocytes. Changes in inflammatory factor expression were analysed by qPCR and immunohistochemistry. KEY RESULTS: Allicin significantly improved the epidermal structure by inhibiting the excessive proliferation and reduced apoptosis of keratinocytes. Furthermore, allicin reduced the secretion of inflammatory cytokines (IL-17A/F, IL-22, IL-12, and IL-20), chemokines (CXCL2, CXCL5, and CCL20), and anti-bacterial peptides (S100a8/9). Mechanistically, allicin directly inhibited the IL-17-induced TRAF6/MAPK/NF-κB and STAT3/NF-κB signalling cascades in keratinocytes, thus breaking the positive inflammatory feedback and alleviating imiquimod-induced psoriasis-like dermatitis in mice. Importantly, topical administration of allicin did not cause skin allergy, and the safety and adaptability of long-term application were verified. CONCLUSIONS AND IMPLICATIONS: Interfering with IL-17 signalling in keratinocytes with allicin is a promising strategy for treating psoriasis, given its safety and effectiveness.