In vivo fluorescence imaging of nanocarriers in near-infrared window II based on aggregation-caused quenching.

Accurate fluorescence imaging of nanocarriers in vivo remains a challenge owing to interference derived mainly from biological tissues and free probes. To address both issues, the current study explored fluorophores in the near-infrared (NIR)-II window with aggregation-caused quenching (ACQ) properties to improve imaging accuracy. Candidate fluorophores with NIR-II emission, ACQ984 (λem = 984 nm) and IR-1060 (λem = 1060 nm), from the aza-BODIPY and cyanine families, respectively, were compared with the commercial fluorophore ICG with NIR-II tail emission and the NIR-I fluorophore P2 from the aza-BODIPY family. ACQ984 demonstrates high water sensitivity with complete fluorescence quenching at a water fraction greater than 50%. Physically embedding the fluorophores illuminates various nanocarriers, while free fluorophores cause negligible interference owing to the ACQ effect. Imaging based on ACQ984 revealed fine structures in the vascular system at high resolution. Moreover, good in vivo and ex vivo correlations in the monitoring of blood nanocarriers can be established, enabling real-time noninvasive in situ investigation of blood pharmacokinetics and dynamic distribution in various tissues. IR-1060 also has a good ACQ effect, but the lack of sufficient photostability and steady post-labeling fluorescence undermines its potential for nanocarrier bioimaging. P2 has an excellent ACQ effect, but its NIR-I emission only provides nondiscriminative ambiguous images. The failure of the non-ACQ probe ICG to display the biodistribution details serves as counterevidence for the improved imaging accuracy by NIR-II ACQ probes. Taken together, it is concluded that fluorescence imaging of nanocarriers based on NIR-II ACQ probes enables accurate in vivo bioimaging and real-time in situ pharmacokinetic analysis.

Large-scale separation of alkaloids from Corydalis decumbens by pH-zone-refining centrifugal partition chromatography and their anticomplement activity.

Centrifugal partition chromatography in the pH-zone-refining mode was successfully applied to the separation of alkaloids from the crude extract of Corydalis decumbens. The experiment was performed with a two-phase solvent system composed of petroleum ether-ethyl acetate-ethanol-water (5:5:3:7, v/v/v/v) where triethylamine (10 mM) was added to the stationary phase and hydrochloric acid (10 mM) to the mobile phase. From 1.6 g of the crude extract, 43 mg protopine, 189 mg (+)-egenine, and 158 mg tetrahydropalmatine were obtained with a purity of 98.2%, 94.6%, and 96.7%, respectively. Tetrahydropalmatine showed an interesting anticomplement effect with CH50 0.11 and AP50 0.25 mg/mL, respectively. In a mechanistic study, tetrahydropalmatine interacted with C1, C3, C4, and C5 components in the complement activation cascade.

FD-1050@NPs-cRGD: A novel NIR-II fluorophore for triple-negative breast cancer imaging.

Triple-negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease that is prone to metastasis and recurrence. It accounts for 15-20% of all breast cancer cases. Surgical resection is effective in removing most of the malignant tissues for non-metastasized tumors; however, some residual tumor tissues would be left, leading to a poor prognosis. Thus, real-time monitoring of surgical resection would be beneficial for the surgical resection of tumors. Although NIR-II fluorescent probe-guided surgical resection has been widely used for other types of diseases, it is not currently used for TNBC in clinical practice. Here, we describe the design and synthesis of a novel NIR-II fluorescent probe, FD-1050@NPs-cRGD, that targets TNBC. We found that it has a high fluorescence quantum efficiency, good stability, and low cytotoxicity. In vivo imaging in mice demonstrated a high tumor signal/normal tissue signal ratio, indicating that FD-1050@NPs-cRGD has great potential to be applied in tumor imaging of TNBC.

Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma.

BACKGROUND: Topical anticancer drugs offer a potential therapeutic modality with high compliance for treating cutaneous squamous cell carcinoma (cSCC). However, the existing topical treatments for cSCC are associated with limited penetrating ability to achieve the desired outcome. Therefore, there remains an urgent requirement to develop drugs with efficient anticancer activity suitable for treating cSCC and to overcome the skin physiological barrier to improve the efficiency of drug delivery to the tumor. RESULTS: We introduced lycorine (LR) into the topical treatment for cSCC and developed a cell-penetrating peptide (CPP)-modified cationic transfersome gel loaded with lycorine-oleic acid ionic complex (LR-OA) (LR@DTFs-CPP Gel) and investigated its topical therapeutic effects on cSCC. The anti-cSCC effects of LR and skin penetration of LR-OA transfersomes were confirmed. Simultaneously, cationic lipids and modification of R5H3 peptide of the transfersomes further enhanced the permeability of the skin and tumor as well as the effective delivery of LR to tumor cells. CONCLUSIONS: Topical treatment of cSCC-xenografted nude mice with LR@DTFs-CPP Gel showed effective anticancer properties with high safety. This novel formulation provides novel insights into the treatment and pathogenesis of cSCC.

Therapeutic action of Kushen recipe extractive and its inhibitory effect on eotaxin in mouse models with contact dermatitis.

BACKGROUND: Treatment of skin allergic diseases remains a challenging research topic. OBJECTIVE: To investigate the effect of Kushen recipe extractive (KS) gel on contact dermatitis (CD) of mouse. METHODS: Allergic contact dermatitis (ACD) model of mouse was established. Immunohistochemical method (ICH) and flow cytometry method (FCM) were used to detect CD4+ and CD8+ T lymphocytes and explore the regulation effect of KS on the immune status of the organism. The expression status of eotaxin tissue was evaluated by real-time polymerase chain reaction (RT-PCR), ICH, and western blotting method. The survival rates of HaCaT cell and Fibroblasts affected by KS were detected by methyl thiazolyl tetrazolium (MTT) method. The inhibitory effect of KS on eotaxin produced by HaCaT cell and FBs induced by TNF-α and interleukin (IL)-4 were evaluated using RT-PCR and enzyme-linked immunosorbent assay methods. The inhibitory effect of KS on nuclear factor-κB (NF-κB) and Signal transducers and activators of transcription 6 (STAT6) activation induced by TNF-α and IL-4 was detected by electrophoretic mobility shift assay and western blotting methods. RESULTS: We confirmed that KS shows favorable therapeutic effect on CD, which can obviously inhibit eotaxin expression and Eosinophils recruitment in allergic skin of mouse, as well as regulate the immune status of the organism. Furthermore, KS and its main effective components can inhibit TNF-α and IL-4 induced upregulation of eotaxin via the two signal transduction pathways, NF-κB and STAT6. CONCLUSIONS: The great importance of traditional Chinese recipe KS is evidenced by its therapeutic effect and mechanism in ACD of mouse.

Vascular Endothelial Growth Factor A VEGFA Inhibition: An Effective Treatment Strategy for Psoriasis.

Psoriasis is an inflammatory skin disease mediated by the immune system and characterized by an inflammatory ring, also known as an epithelial immune microenvironment (EIME). The interaction between the epithelial tissue of the skin and the immune system has a crucial role in the immune cycle of psoriasis. Although the formation of new blood vessels in skin lesions provides energy support for the proliferation of epidermal keratinocytes, the role of angiogenesis in psoriasis has not been extensively studied. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis that has an important role in the development of psoriasis. VEGFA promotes angiogenesis and directly stimulates epidermal keratinocytes and infiltrating immune cells, thus contributing to the progression of psoriasis. Measuring VEGFA levels to identify angiogenic characteristics in psoriasis patients may be a predictive biomarker for disease severity and response to anti-angiogenic therapy. Clinical data have shown that anti-angiogenic therapy can improve skin lesions in psoriasis patients. Therefore, this study aimed to uncover the underestimated role of blood vessels in psoriasis, explore the relationship between VEGFA and keratinocytes in the EIME, and inspire innovative drug therapies for the treatment of psoriasis.

Physical therapy in diabetic foot ulcer: Research progress and clinical application.

Diabetes foot ulcer (DFU) is one of the most intractable complications of diabetes and is related to a number of risk factors. DFU therapy is difficult and involves long-term interdisciplinary collaboration, causing patients physical and emotional pain and increasing medical costs. With a rising number of diabetes patients, it is vital to figure out the causes and treatment techniques of DFU in a precise and complete manner, which will assist alleviate patients' suffering and decrease excessive medical expenditure. Here, we summarised the characteristics and progress of the physical therapy methods for the DFU, emphasised the important role of appropriate exercise and nutritional supplementation in the treatment of DFU, and discussed the application prospects of non-traditional physical therapy such as electrical stimulation (ES), and photobiomodulation therapy (PBMT) in the treatment of DFU based on clinical experimental records in ClinicalTrials.gov.

Converting Tretinoin into Ionic Liquids for Improving Aqueous Solubility and Permeability across Skin.

PURPOSE: The aim of this study is to convert tretinoin (Tr), an active pharmaceutical ingredient (API), into ionic liquid for improving aqueous solubility and permeability of Tr in transdermal drug delivery applications. METHODS: Three ionic liquids of Tr (TrILs) were synthesized through neutralization reactions, which were characterized to confirm the compositions and ionic interactions. The in vitro drug release studies and skin penetration tests were carried out to assess the performance of formulations containing TrILs. RESULTS: The TrIL formed by choline and Tr at the molar ratio of 2:1 (2[Ch][Tr]), was found to have prominent solubility, stability as well as permeability. In contrast with the insoluble Tr, 2[Ch][Tr] presented as clear and transparent aqueous solution even after diluted to 14%. The aqueous solution of 2[Ch][Tr] demonstrated better permeation effect, of which the solution with 20% of 2[Ch][Tr] showed the optimal delivery efficiency in both epidermis (2.09 ± 0.18‰) and dermis (3.31 ± 0.48‰), realizing the improvement on the permeability of API. Meanwhile, TrILs can be easily fabricated as o/w emulsions as transdermal formulation. The emulsions are also able to improve the skin permeability of Tr, though the enhanced effect is inferior to TrILs solutions. CONCLUSIONS: Ionic liquid technology can be used to improve solubility and permeability of Tr, providing a high potential strategy for the development of topical formulations and the desired transdermal application of drugs.

Bioassay-Guided Isolation of New Flavonoid Glycosides from Platanus × acerifolia Leaves and Their Staphylococcus aureus Inhibitory Effects.

Despite the rapid advances in drug R&D, there is still a huge need for antibacterial medications, specifically for the methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the research where a viable class of MRSA inhibitors was found in the species Platanus occidentalis, a S. aureus inhibition screening-guided phytochemical reinvestigation on Platanus × acerifolia (London plane tree) leaves were performed with four flavonoid glycosides garnered, including two new compounds, quercetin-3-O-α-l-(2″-E-p-coumaroyl-3″-Z-p-coumaroyl)-rhamnopyranoside (E,Z-3'-hydroxyplatanoside, 1) and quercetin-3-O-α-l-(2″-Z-p-coumaroyl-3″-E-p-coumaroyl)-rhamnopyranoside (Z,E-3'-hydroxyplatanoside, 2). All of the isolates showed significant S. aureus ATCC 25904 inhibitory activity with MICs ranging from 4 to 64 µg/mL, suggesting the potential of discovering drug leads for the control of S. aureus from such a rich, urban landscaping plant in the Platanus genus.

Regulation of eotaxin expression in skin allergic diseases.

Introduction: As a key chemotactic factor during Eos recruitment on the allergic inflammation site, eotaxin is regarded as one of the important therapeutic targets. Aim: To address the expression and regulation mechanism of eotaxin, which constitutes an important procedure in skin allergic disease and a target for drug therapy. Material and methods: An allergic contact dermatitis (ACD) model of mouse was established. Immunohistochemical method (ICH) and flow cytometry method (FCM) were used to determine the amounts of CD4+ and CD8+ T cells and their ratios. The eotaxin mRNA and protein were evaluated by real-time PCR, ICH and western-blotting method. Nuclear factor-κB (NF-κB) nuclear translocation and STAT6 phosphorylation were studied by EMSA and western-blotting methods. Results: We confirmed that both CD4+ and CD8+ T cells in mouse blood and tissue increased during the allergic process, FBs was the main source for eotaxin under the allergic condition. Both TNF-α and IL-4 showed synergic effects on the up-regulation of eotaxin mRNA and protein in KC and FBs. Eotaxin can be expressed via NF-κB and STAT6 transcription after KC and FBs were stimulated by TNF-α and IL-4. Conclusions: The obvious up-regulation of eotaxin expression in skin tissue of the mouse ACD model was confirmed, the exact expression site and dynamic process was determined both in vivo and in vitro. The eotaxin expression ability of FBs outperformed that of KC, and eotaxin expression can be regulated by TNF-α and IL-4 via NF-κB and STAT6. The overall findings may pave the way for discovering targets for new drugs and new therapeutic drugs for treating allergic diseases.

Immunotherapy Strategy Targeting Programmed Cell Death Ligand 1 and CD73 with Macrophage-Derived Mimetic Nanovesicles to Treat Bladder Cancer.

Combination immunotherapy is a promising strategy to remove the inhibitory effect of the tumor microenvironment on immune effector cells, improving the efficacy of immune checkpoint inhibitor treatment in bladder cancer. However, it is challenging to deliver multiple drugs to the tumor tissue effectively and simultaneously to ensure optimal therapeutic effects. Macrophage-derived exosome-mimetic nanovesicles (EMVs) were designed and validated as a nanoplatform for coloading and delivery of the CD73 inhibitor (AB680) and the monoclonal antibody to programmed cell death ligand 1 (aPDL1). The tumor-targeting, biosafety, and therapeutic effects of these nanocomplexes (AB680@EMVs-aPDL1), as a combined immunotherapy strategy for bladder cancer, were assessed in vitro and in vivo. Our results indicate that the nanodrug system was highly stable, provided adequate biosafety, and enhanced tumor targeting in a mouse model of bladder cancer. Moreover, the CD73 inhibitor reduced extracellular adenosine production, and the combination therapy significantly promoted the activation and infiltration of cytotoxic T-lymphocytes, which helped to optimally suppress tumor growth and extend median survival in vivo. Therefore, using EMVs to deliver a combination of aPDL1 and the CD73 inhibitor may be a useful combined immunotherapy strategy for treating bladder cancer.

Enhanced immunity and hemocytes proliferation by three immunostimulants in tri-spine horseshoe crab Tachypleus tridentatus.

Tachypleus amebocyte lysate (TAL) is crucial in medical testing, but its industry in China has been restricted due to the decline of horseshoe crab population in recent years. Exploring methods of enhancing immunity and rapid hemocytes proliferation is urgent for the industrial horseshoe crab culture. In this study, ß-glucan (G), peptidoglycan (P), and squalene (S) were injected to horseshoe crabs at two concentrations (5 and 10 mg/kg), in order to compare their effects on total hemocyte count (THC), reactive oxygen species (ROS), and non-specific immune enzyme activities. Results showed that the THC, superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were significantly increased by three immunostimulants at different points of time; ROS was significantly increased except at two squalene groups; lysozyme (LZM) and alkaline phosphatase (AKP) activity were increased except at low dose (5 mg/kg) squalene group; malondialdehyde (MDA) activity was decreased in all treatments; and hemocyanin concentration (HC) changed little during the experiment. At the 48th hour, THC, ROS, SOD, CAT, T-AOC, LZM, and AKP activities were significantly higher in the two peptidoglycan groups than those in the control group; the low dose ß-glucan and squalene groups showed significantly higher SOD and CAT, but their THC and AKP were not significantly different from those of the control group. In general, all three immunostimulants stimulated the hemolymph parameters of horseshoe crabs, notably, peptidoglycan could significantly increase the THC and enzyme activities, suggesting that peptidoglycan can be developed as an efficient immunostimulant for horseshoe crabs.

Biodegradable stearylated peptide with internal disulfide bonds for efficient delivery of siRNA in vitro and in vivo.

RNA-based delivery system for cancer therapy remains a challenge. In this study, a stearyl-peptide (SHR) was synthesized using arginine, histidine, cysteine, and stearyl moieties. Further, the stearyl-peptides were cross-linked by disulfide bonds to obtain cross-linked polypeptides (SHRss) with different molecular weight (SHRss1, SHRss2, SHRss3, SHRss4). The SHRss could effectively condense small interfering RNA (siRNA) into polyplexes with a hydrodynamic size of 100-300 nm and zeta potential of 20-40 mV. Flow cytometry and confocal laser scanning microscope studies revealed high cellular uptake and rapid dissociation behavior of SHRss2/siRNA complexes. Long-lasting high concentration of siRNA in cytoplasm was observed even at 24 h after SHRss2/Cy3-siRNA transfection. Compared with SHR, the SHRss showed much improved siRNA interference efficiency targeting luciferase on Luc-Hela cells. Moreover, SHRss2 exhibited higher interference efficiency and slower decay rate on Luc-Hela cells than Lipofectamine 2000 and SHR. In addition, much weaker expression of red fluorescence protein was also observed on SHRss2/simCh-treated mCherry-HEK293 cells than Lipofectamine 2000 and SHR. The SHRss did not induce cytotoxicity at siRNA concentrations of 25-200 nM under transfection. The in vivo studies demonstrated the gene interference efficiency of SHRss2/siRNA complexes. Our studies indicated that the SHRss are promising and efficient nonviral vectors for siRNA delivery.

Cordycepin Ameliorates Psoriasis-Like Skin Lesion by Regulating p53/MDM2 Feedback Loop.

Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.

Ionic Liquid Pretreatment Enhances Skin Penetration of 5-Aminolevulinic Acid: A Promising Scheme for Photodynamic Therapy for Acne Vulgaris.

Acne vulgaris is one of the most prevalent skin disorders; it affects up to 85% of adolescents and often persists into adulthood. Topical 5-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides an alternative treatment for acne; however, its efficacy is greatly undermined by the limited skin permeability of ALA. Herein, biocompatible ionic liquids (ILs) based on aliphatic acid/choline were employed to enhance the dermal delivery of ALA, thereby improving the efficacy of PDT. In addition to the one-step delivery of ALA by utilizing ILs as carriers, a two-step strategy of pretreating the skin with blank ILs, followed by the administration of free ALA, was employed to test the IL-facilitated dermal delivery of ALA in vitro. The cumulative permeation of ALA through the excised rat skin after IL pretreatment was significantly greater than that in the untreated group, the 20% dimethyl sulfoxide (DMSO) penetration enhancer group, and the one-step group. The penetration efficiency was influenced by formulation and treatment factors, including the type of IL, pretreatment duration, water content in the ILs, and concentration of ALA. In rats, IL pretreatment facilitated faster, greater, and deeper ALA-induced protoporphyrin IX (PpIX) accumulation. Moreover, the IL pretreatment regimen significantly improved the efficacy of ALA-based PDT against acne vulgaris in a rat ear model. The model IL choline citrate ([Ch]3[Cit]1) had a moderate effect on the skin barrier. Trans-epidermal water loss could be recovered 1 h after IL treatment, but no irritation to the rat skin was detected after 7 days of consecutive treatment. It was concluded that biocompatible IL pretreatment enhances the penetration of ALA and thus facilitates the transformation of PpIX and improves the efficacy of PDT against acne vulgaris.

Adoptive cell therapy for solid tumors beyond CAR-T: Current challenges and emerging therapeutic advances.

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) is a highly specific anti-tumor immunotherapy that has shown promise in the treatment of hematological malignancies. However, there has been a slow progress toward the treatment of solid tumors owing to the complex tumor microenvironment that affects the localization and killing ability of the CAR cells. Solid tumors with a strong immunosuppressive microenvironment and complex vascular system are unaffected by CAR cell infiltration and attack. To improve their efficacy toward solid tumors, CAR cells have been modified and upgraded by "decorating" and "pruning". This review focuses on the structure and function of CARs, the immune cells that can be engineered by CARs and the transformation strategies to overcome solid tumors, with a view to broadening ideas for the better application of CAR cell therapy for the treatment of solid tumors.

Staphylococcus aureus biofilm: Formulation, regulatory, and emerging natural products-derived therapeutics.

Staphylococcus aureus can readily form biofilm which enhances the drug-resistance, resulting in life-threatening infections involving different organs. Biofilm formation occurs due to a series of developmental events including bacterial adhesion, aggregation, biofilm maturation, and dispersion, which are controlled by multiple regulatory systems. Rapidly increasing research and development outcomes on natural products targeting S. aureus biofilm formation and/or regulation led to an emergent application of active phytochemicals and combinations. This review aimed at providing an in-depth understanding of biofilm formation and regulation mechanisms for S. aureus, outlining the most important antibiofilm strategies and potential targets of natural products, and summarizing the latest progress in combating S. aureus biofilm with plant-derived natural products. These findings provided further evidence for novel antibiofilm drugs research and clinical therapies.

The epidermal lipid-microbiome loop and immunity: Important players in atopic dermatitis.

BACKGROUND: The promotion of epidermal barrier dysfunction is attributed to abnormalities in the lipid-microbiome positive feedback loop which significantly influences the imbalance of the epithelial immune microenvironment (EIME) in atopic dermatitis (AD). This imbalance encompasses impaired lamellar membrane integrity, heightened exposure to epidermal pathogens, and the regulation of innate and adaptive immunity. The lipid-microbiome loop is substantially influenced by intense adaptive immunity which is triggered by abnormal loop activity and affects the loop's integrity through the induction of atypical lipid composition and responses to dysregulated epidermal microbes. Immune responses participate in lipid abnormalities within the EIME by downregulating barrier gene expression and are further cascade-amplified by microbial dysregulation which is instigated by barrier impairment. AIM OF REVIEW: This review examines the relationship between abnormal lipid composition, microbiome disturbances, and immune responses in AD while progressively substantiating the crosstalk mechanism among these factors. Based on this analysis, the "lipid-microbiome" positive feedback loop, regulated by immune responses, is proposed. KEY SCIENTIFIC CONCEPTS OF REVIEW: The review delves into the impact of adaptive immune responses that regulate the EIME, driving AD, and investigates potential mechanisms by which lipid supplementation and probiotics may alleviate AD through the up-regulation of the epidermal barrier and modulation of immune signaling. This exploration offers support for targeting the EIME to attenuate AD.

Transdermal delivery of Fn14 siRNA using a novel composite ionic liquid for treatment of psoriasis-like skin lesions.

Psoriasis is a chronic inflammatory skin disease characterised by the abnormal proliferation of keratinocytes and dysregulation of immune cells. The upregulation of fibroblast growth factor-inducible molecule 14 (Fn14) in psoriatic lesions has been linked to the development of psoriasis. Transdermal delivery of siRNAs for Fn14 inhibition is challenging. In this study, we developed a composite ionic liquid (CIL) for the transdermal delivery of Fn14 siRNA (siFn14) into keratinocytes, with the aim of modulating the inflammatory response associated with psoriasis. The results showed that CIL-siFn14 effectively suppressed Fn14 expression, resulting in a reduction in both the Psoriasis Area and Severity Index (PASI) score and skin thickness. Furthermore, CIL-siFn14 effectively inhibited the abnormal proliferation of keratinocytes, decreased the production of inflammatory factors associated with psoriasis, prevented the over-activation of CD4+ and CD8+ T cells, and restored the balance of Type 1 T helper (Th1), Th2, Th17 and Treg cells. In conclusion, our findings unveiled the critical role of Fn14 in the pathogenesis of psoriasis and demonstrated the potential of CIL-siFn14 as a novel and effective topical treatment for its management.

ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms.

Renal ischemia reperfusion (IR) injury is a prevalent inflammatory nephropathy in surgeries such as renal transplantation or partial nephrectomy, damaging renal function through inducing inflammation and cell death in renal tubules. Mesenchymal stromal/stem cell (MSC)-based therapies, common treatments to attenuate inflammation in IR diseases, fail to exhibit satisfying effects on cell death in renal IR. In this study, we prepared MSC-derived exosome mimetics (EMs) carrying the mammalian target of the rapamycin (mTOR) agonist to protect kidneys in proinflammatory environments under IR conditions. The thioketal-modified EMs carried the mTOR agonist and bioactive molecules in MSCs and responsively released them in kidney IR areas. MSC-derived EMs and mTOR agonists protected kidneys synergistically from IR through alleviating inflammation, apoptosis, and ferroptosis. The current study indicates that MSC-TK-MHY1485 EMs (MTM-EM) are promising therapeutic biomaterials for renal IR injury.