A green and simple method for enrichment of major diterpenoids from the buds of Wikstroemia chamaedaphne with macroporous resins and their activation of latent human immunodeficiency virus activity.

In this study, a green and efficient enrichment method for the four majors active diterpenoid components: pimelotide C, pimelotide A, simplexin, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate in the buds of Wikstroemia chamaedaphne was established using macroporous resin chromatography. The adsorption and desorption rates of seven macroporous resins were compared using static tests. The D101 macroporous resin exhibited the best performance. Static and dynamic adsorption tests were performed to determine the enrichment and purification of important bioactive diterpenoids in the buds of W. chamaedaphne. Diterpenoid extracts were obtained by using D101 macroporous resin from the crude extracts of W. chamaedaphne. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated that most of the diterpenoids were enriched in diterpenoid extracts. These results confirmed that diterpenoids in the buds of W. chamaedaphne could be enriched using macroporous resin technology, and the enriched diterpenoid extracts showed more efficient activation of the latent human immunodeficiency virus. This study provides a novel strategy for discovering efficient and low-toxicity latency-reversing agents and a potential basis for the comprehensive development and clinical application of the buds of W. chamaedaphne.

Chemical constituents from the leaves and branches of Wikstroemia chamaedaphne with their activation of latent HIV activities.

A new compound, named coniferin B (1), and fourteen known compounds were purified and identified from the leaves and branches of Wikstroemia chamaedaphne Meisn. Their chemical structures were elucidated through analyzing spectroscopic and HRESIMS data. Compounds 2, 3, 5, 7-9, 11, and 13 were isolated from this plant for the first time. All compounds were assayed for cytotoxicity and activation of latent HIV activity on NH2 cells. The results showed that all compounds did not produce cytotoxicity at 10.0 µM and compounds 1, 9-11 showed weak activating activity with activation folds of 4.88, 7.14, 5.3, and 6.97, respectively.

Identification of m6A-Related Biomarkers in Systemic Lupus Erythematosus: A Bioinformation-Based Analysis.

Background: Systemic Lupus Erythematosus (SLE), a prototypical autoimmune disorder, presents a challenge due to the absence of reliable biomarkers for discerning organ-specific damage within SLE. A growing body of evidence underscores the pivotal involvement of N6-methyladenosine (m6A) in the etiology of autoimmune conditions. Methods: The datasets, which primarily encompassed the expression profiles of m6A regulatory genes, were retrieved from the Gene Expression Omnibus (GEO) repository. The optimal model, selected from either Random Forest (RF) or Support Vector Machine (SVM), was employed for the development of a predictive nomogram model. To identify pivotal genes associated with SLE, a comprehensive screening process was conducted utilizing LASSO, SVM-RFE, and RF techniques. Within the realm of SLE susceptibility, Weighted Gene Co-expression Network Analysis (WGCNA) was harnessed to delineate relevant modules and hub genes. Additionally, MeRIP-qPCR assays were performed to elucidate key genes correlated with m6A targets. Furthermore, a Mendelian randomization study was conducted based on genome-wide association studies to assess the causative influence of MMP9 on ischemic stroke (IS), which is not only a severe cerebrovascular event but also a common complication of SLE. Results: Twelve m6A regulatory genes was identified, demonstrating statistical significance (p < 0.05) and utilized for constructing a nomogram model using the RF algorithm. EPSTI1, USP18, HP, and MMP9, as the hub genes, were identified. MMP9 uniquely correlates with m6A modification and was causally linked to an increased risk of IS, as indicated by our inverse variance weighting analysis showing an odds ratio of 1.0134 (95% CI=1.0004-1.0266, p = 0.0440). Conclusion: Our study identified twelve m6A regulators, shedding light on the molecular mechanisms underlying SLE risk genes. Importantly, our analysis established a causal relationship between MMP9, a key m6A-related gene, and ischemic stroke, a common complication of SLE, thereby providing critical insights for presymptomatic diagnostic approaches.

Ferroptosis in peripheral blood mononuclear cells of systemic lupus erythematosus.

OBJECTIVES: To investigate the evidence of ferroptosis in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE). METHODS: PBMCs were collected from 30 patients diagnosed as SLE and without any standardised treatment previously and 10 healthy controls. Meanwhile the clinical and laboratory data were collected. The intracellular Fe2+, reactive oxygen species (ROS) and lipid peroxidation (LPO) were detected by fluorescence probe and flow cytometry. The morphology of cells and intracellular organelles were observed by transmission electron microscopy. RT-qPCR and Western blot were applied to compare the expression of GPX4 in PBMCs. RESULTS: The concentration of Fe2+, levels of ROS and LPO in PBMCs from SLE patients were significantly higher than those in healthy controls (p<0.05), and significant differences between the two groups were observed in CD14+ monocytes, CD19+B cells, and CD56+ NK cells respectively. The more prominent differences were observed in SLE patients with renal involvement, liver injury and higher disease activity score. There was no significant difference in GPX4 mRNA expression between SLE patients and healthy controls, however GPX4 protein expression was significantly lower in SLE patients compared to healthy controls, with a negative correlation with the SLE disease activity index. Transmission electron microscopy revealed typical morphological features of ferroptosis such as decreased mitochondrial volume, increased mitochondrial membrane density, and disappearance of mitochondrial cristas. CONCLUSIONS: Ferroptosis occurred more frequently in PBMCs of SLE patients than healthy controls, including CD14+ monocytes, CD19+B cells, CD56+ NK cells, and so on, with negative association with SLE disease activity, which indicated the correlation between ferroptosis with the pathogenesis of SLE.

The impact of the COVID-19 pandemic on SLE.

Little is known about the association between coronavirus disease 2019 (COVID-19) and autoimmune diseases, especially in the case of systemic lupus erythematosus (SLE). SLE patients met with many questions during the pandemic in COVID-19, such as how to minimize risk of infection, the complex pathological features and cytokine profiles, diagnosis and treatment, rational choice of drugs and vaccine, good nursing, psychological supervision, and so on. In this study, we review and discuss the multifaceted effects of the COVID-19 pandemic on patients living with SLE using the available literature. Cross-talk in implicated inflammatory pathways/mechanisms exists between SLE and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and SARS-CoV-2 displays similar clinical characteristics and immuno-inflammatory responses to SLE. Current epidemiological data inadequately assess the risk and severity of COVID-19 infection in patients with SLE. More evidence has shown that hydroxychloroquine and chloroquine cannot prevent COVID-19. During the pandemic, patients with SLE had a higher rate of hospitalization. Vaccination helps to reduce the risk of infection. Several therapies for patients with SLE infected with COVID-19 are discussed. The cases in the study can provide meaningful information for clinical diagnosis and management. Our main aim is to help preventing infection and highlight treatment options for patients with SLE infected with COVID-19.

CircPTPN22 modulates T-cell activation by sponging miR-4689 to regulate S1PR1 expression in patients with systemic lupus erythematosus.

BACKGROUND: Circular RNAs are involved in autoimmune disease pathogenesis. Our previous study indicated that circPTPN22 is involved in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, but the underlying mechanisms remain unclear. METHODS: First, the expression of circPTPN22 was detected by real-time PCR and western blotting. After overexpression or knockdown of circPTPN22, the proliferation of Jurkat cells was detected by the CCK-8 assay, and the apoptosis of Jurkat cells was detected by flow cytometry. In addition, the relationship between circPTPN22-miR-4689-S1PR1 was confirmed by bioinformatic analyses, fluorescence in situ hybridization assays, RNA-binding protein immunoprecipitation, and dual luciferase reporter assays. RESULTS: We found that circPTPN22 expression was downregulated in the PBMCs of SLE patients compared to those of healthy controls. Overexpression of circPTPN22 increased proliferation and inhibited apoptosis of Jurkat T cells, whereas knockdown of circPTPN22 exerted the opposite effects. CircPTPN22 acts as a miR-4689 sponge, and S1PR1 is a direct target of miR-4689. Importantly, the circPTPN22/miR-4689/S1PR1 axis inhibited the secretion of TNF-α and IL-6 in Jurkat T cells. CONCLUSIONS: CircPTPN22 acts as a miR-4689 sponge to regulate T-cell activation by targeting S1PR1, providing a novel mechanism for the pathogenesis of SLE.

Featured immune characteristics of COVID-19 and systemic lupus erythematosus revealed by multidimensional integrated analyses.

BACKGROUND: Coronavirus disease 2019 (COVID-19) shares similar immune characteristics with autoimmune diseases like systemic lupus erythematosus (SLE). However, such associations have not yet been investigated at the single-cell level. METHODS: We integrated and analyzed RNA sequencing results from different patients and normal controls from the GEO database and identified subsets of immune cells that might involve in the pathogenesis of SLE and COVID- 19. We also disentangled the characteristic alterations in cell and molecular subset proportions as well as gene expression patterns in SLE patients compared with COVID-19 patients. RESULTS: Key immune characteristic genes (such as CXCL10 and RACK1) and multiple immune-related pathways (such as the coronavirus disease-COVID-19, T-cell receptor signaling, and MIF-related signaling pathways) were identified. We also highlighted the differences in peripheral blood mononuclear cells (PBMCs) between SLE and COVID-19 patients. Moreover, we provided an opportunity to comprehensively probe underlying B-cell‒cell communication with multiple ligand-receptor pairs (MIF-CD74+CXCR4, MIF-CD74+CD44) and the differentiation trajectory of B-cell clusters that is deemed to promote cell state transitions in COVID-19 and SLE. CONCLUSIONS: Our results demonstrate the immune response differences and immune characteristic similarities, such as the cytokine storm, between COVID-19 and SLE, which might pivotally function in the pathogenesis of the two diseases and provide potential intervention targets for both diseases.

Higher House Dust Mite-Specific IgE Levels among Chronic Spontaneous Urticaria Patients May Implicate Higher Basophil Reactivity.

INTRODUCTION: Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. METHODS: Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. RESULTS: HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. CONCLUSION: CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.

A unique ratiometric fluorescent probe for detection of SO2 derivatives in living cells and real food samples.

Abnormal levels of SO2 in organisms can cause cardiovascular disease and respiratory allergies. In addition, the amount of SO2 derivatives used as food preservatives is strictly controlled, and excessive addition can also be harmful to health. Therefore, it is essential to develop a highly sensitive method for the detection of SO2 and its derivatives in biological systems and real food samples. In this work, a new fluorescent probe (TCMs) with high selectivity and sensitivity for the detection of SO2 derivatives was reported. The TCMs could quickly identify SO2 derivatives. It has been successfully used to detect exogenous and endogenous SO2 derivatives. Furthermore, the TCMs has high sensitivity to SO2 derivatives in food samples. Moreover, the prepared test strips could be evaluated for the content of SO2 derivatives in aqueous solutions. This work provides a potential chemical tool to detect SO2 derivatives in living cells and real food samples.

Discovering the Mechanisms of Oleodaphnone as a Potential HIV Latency-Reversing Agent by Transcriptome Profiling.

Latent HIV is a key factor that makes AIDS difficult to cure. Highly effective and specific latent HIV activators can effectively activate latent HIV, and then combined with antiretroviral therapy to achieve a functional cure of AIDS. Here, four sesquiterpenes (1-4) including a new one (1), five flavonoids (5-9) including three biflavonoid structures, and two lignans (10 and 11) were obtained from the roots of Wikstroemia chamaedaphne. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configuration of 1 was determined by experimental electronic circular dichroism. NH2 cell model was used to test the activity of these 11 compounds in activating latent HIV. Oleodaphnone (2) showed the latent HIV activation effect as well as the positive drug prostratin, and the activation effect was time- and concentration-dependent. Based on transcriptome analysis, the underlying mechanism was that oleodaphnone regulated the TNF, C-type lectin receptor, NF-κB, IL-17, MAPK, NOD-like receptor, JAK-Stat, FoxO, and Toll-like receptor signaling pathways. This study provides the basis for the potential development of oleodaphnone as an effective HIV latency-reversing agent.

Phillygenin Attenuated Colon Inflammation and Improved Intestinal Mucosal Barrier in DSS-induced Colitis Mice via TLR4/Src Mediated MAPK and NF-κB Signaling Pathways.

Ulcerative colitis (UC) is a chronic, relapsing, and nonspecific inflammatory bowel disease (IBD). Phillygenin (PHI), a natural bioactive ingredient, isolated from Forsythiae Fructus, exhibits anti-inflammatory, anti-oxidative, and hepatoprotective activities. However, few reports provide direct evidence on the efficacy of PHI in improving colitis mice. The present study elucidated that the symptoms of DSS-induced colitis mice were alleviated after PHI administration, including body weight loss, the disease activity index, colon length shortening, colonic pathological damage, splenomegaly, and hepatomegaly. PHI treatment improved the intestinal mucosal barrier by protecting goblet cells, promoting gene expressions of Clca1, Slc26a3, and Aqp8, increasing tight junction proteins (TJs), and reducing epithelial cell apoptosis. In addition, the levels of oxidative stress (MPO, SOD, and MDA) and inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-10) were reversed by PHI in colitis mice. According to transcriptome and network pharmacology analysis, inflammatory pathway might be an important mechanism for PHI to improve colitis. Western blotting displayed that the PHI inhibited the activation of tyrosine kinase Src mediated by TLR4, and then reduced the phosphorylation of downstream proteins p38, JNK, and NF-κB in colitis mice. In summary, our results suggested that PHI might be an appropriate and effective drug candidate to protect colitis.

Regulation of the alkyl chain of fluorescent probes to selectively target the cell membrane or mitochondria in living cells.

The visualization of cell membrane and mitochondrial behavior in living cells is of great life science value, but challenging due to the lack of ideal probes. In this work, two novel fluorescent probes based on different lengths of alkyl chains were reported for selective targeting of cell membranes or mitochondria of living cells. The probe CTM (1-Octadecyl-4-[9-ethyl-6-(diphenylamino)-9H-carbazol-3-yl] pyridinium) achieved cell membrane-specific staining in cells. Moreover, the probe CTM could monitor cell membrane damage through subcellular migration. Once the cell membrane was damaged, the probe CTM migrated into the mitochondria as a signal reporter. In addition, the probe MTM (1-Dodecly-4-[9-ethyl-6-(diphenylamino)-9H-carbazol-3-yl] pyridinium) with the shorter alkyl chain bearing the same skeleton structure penetrated the cell membrane and exhibited high affinity to mitochondria. This work will provide a useful tool to visualize the behavior of cell membranes and mitochondria in living cells.

miR-31-5p Regulates Type I Interferon by Targeting SLC15A4 in Plasmacytoid Dendritic Cells of Systemic Lupus Erythematosus.

Background: Plasmacytoid dendritic cells (pDCs) are the main producers of type I interferon (IFN-I), and the excessive production of IFN-I is a hallmark of systemic lupus erythematosus (SLE). Both SLC15A4 and miR-31-5p are SLE susceptibility-related genes, and SLC15A4 has been implicated an important role in endolysosomal toll-like receptor (TLR) activation in pDCs. However, whether miR-31-5p exerts a regulating effect on SLC15A4 expression in pDCs is unclear. Methods: The expression of SLC15A4 and miR-31-5p in peripheral blood mononuclear cells (PBMCs) of SLE patients was measured by RT-qPCR analyses. The quantitative analysis of IFN-α secretion in the patients' serum was performed by ELISA assay. Luciferase-reporter assay was applied to confirm the interaction between miR-31-5p and SLC15A4. The expression of miR-31-5p, SLC15A4 and IFN-stimulated genes (ISGs, such as MX1, OAS1 and IFIT3) was detected by Western blot and RT-qPCR assays and further IRF5 phosphorylation was evaluated by immunofluorescence after transfected with miR-31-5p mimics or inhibitor in THP-1 and CAL-1 cells. Results: The expression of miR-31-5p was downregulated and negatively correlated with the overexpression of SLC15A4 in PBMCs of SLE patients. In addition to this, the secretion of IFN-α was overexpressed in sera of SLE and positively correlated with SLC15A4 level. We found that miR-31-5p directly targeted SLC15A4 and negatively regulated the expression of SLC15A4 in THP-1 and CAL-1 cells. In vitro inhibition of miR-31-5p increased the phosphorylation of IRF5 and the induction of ISGs stimulated by R848, overexpression of miR-31-5p get the reverse results. Conclusion: miR-31-5p might involve in SLE pathogenesis through regulating IFN-I expression by negatively regulating SLC15A4 to increase the levels of IFN-α and ISGs in pDCs.

Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne.

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Better detoxifying effect of ripe forsythiae fructus over green forsythiae fructus and the potential mechanisms involving bile acids metabolism and gut microbiota.

Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called "Qingqiao" and "Laoqiao" referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.

Dimeric sesquiterpenoids and anti-inflammatory constituents of Sarcandra glabra.

Three novel dimeric sesquiterpenoids named sarglanoids A-C (1-3), two undescribed monomeric sesquiterpenoids named sarglanoids D (4) and E (5), and seven known compounds (6-12), were isolated and characterized from Sarcandra glabra. Compound 1 represents the first heterodimeric sesquiterpenoid composed of a eudesmane and an eremophilane moiety. Compound 2 possesses two eremophilane monomers featuring an undescribed dimerization pattern. Compound 3 is a symmetric eudesmane dimer with a rare 1,4-epoxy bridge. The structures of 1-5 were fully identified by spectroscopic methods and single-crystal X-ray diffraction experiments. Compounds 3 and 6 suppressed the LPS-triggered inflammatory responses in RAW 264.7 cells.

Efficacy and safety of ebastine dose escalation in chronic urticaria: A prospective study.

The second-generation antihistamines at licensed doses are first-line treatment in urticaria and up-dosing is recommended as second-line treatment. To assess the efficacy and safety of escalated doses of ebastine in patients with chronic urticaria (CU), we designed this study. Recruited patients with CU were treated with increasing doses of ebstine. Treatment started at the daily dose of 10 mg. The symptom is assessed weekly, and if there is no significant improvement, the dose is increased from 10 mg to 20 mg, and if still no significant improvement, up to 40 mg. Pruritus, number, diameter, duration and frequency of wheals, and adverse reactions were assessed. One hundred and forty (76.50%) patients achieved marked effect with ebastine 10 mg/day, 27 (14.75%) patients with ebastine 20 mg/day and 13 (7.10%) patients with ebastine 40 mg/day, while 3(1.64%) patients did not get marked effect. There was no significant difference of effect between factitious urticaria, CSU, cholinergic urticaria and CSU with factitious urticaria in different dose (all p > 0.05). Common adverse reactions of ebstine treatment, included dry mouth, somnolence, tiredness and headache, were mild or moderate. There was no significant difference between the degree score of dry mouth with different doses of ebastine, and the same to somnolence, tiredness and headache (all p > 0.05). Doses escalation of ebastine should be effective in treatment of factitious urticaria, CSU and cholinergic urticaria with poorly treated by standard of double doses. Increasing ebastine dose did not increase the incidence of adverse reactions.

Increased Frequency of Circulating Classical Monocytes in Patients with Rosacea.

PURPOSE: Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment. PATIENTS AND METHODS: We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea, while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of C-C chemokine receptor 2 (CCR2) on monocytes and plasma levels of CC-chemokine ligand 2 (CCL2), high mobility group box-1 (HMGB-1), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were measured in HC and rosacea patients before and after treatment. RESULTS: The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythematotelangiectatic rosacea (ETR) and ETR-papulopustular rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phymatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1ß and TNF-α in patients than in HC, which all significantly decreased after treatment. CONCLUSION: Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea.

Discovering the Mechanisms of Wikstroelide E as a Potential HIV-Latency-Reversing Agent by Transcriptome Profiling.

The discovery of efficient and specific HIV-latency-reversing agents is critical for HIV therapy. Here, we developed wikstroelide E, a daphnane diterpene from the buds of Wikstroemia chamaedaphne, as a potential HIV-latency-reversing agent that is 2500-fold more potent than the drug prostratin. Based on transcriptome analysis, the underlying mechanism was that wikstroelide E regulated the MAPK, PI3K-Akt, JAK-Stat, TNF, and NF-κB signaling pathways. We clearly demonstrated that wikstroelide E reversed latent HIV infection by activating PKC-NF-κB signals, serving as a proxy for verifying the transcriptome data. Strikingly, the Tat protein contributes to the robust activation of latent HIV in wikstroelide-E-treated cells, producing an unexpected latency-reversing effect against latent HIV. This study provides the basis for the potential development of wikstroelide E as an effective HIV-latency-reversing agent.