Single-Cell Analysis in Blood Reveals Distinct Immune Cell Profiles in Gouty Arthritis.

Gout is a chronic disease caused by monosodium urate crystal deposition. Previous studies have focused on the resident macrophage, infiltrating monocyte, and neutrophil responses to monosodium urate crystal, yet the mechanisms of the potential involvement of other immune cells remain largely unknown. In this study, we enrolled seven gout patients and five age-matched healthy individuals and applied single-cell mass cytometry to study the distribution of immune cell subsets in peripheral blood. To our knowledge, our study reveals the immune cell profiles of gout at different stages for the first time. We identified many immune cell subsets that are dysregulated in gout and promote gouty inflammation, especially those highly expressing CCR4 and OX40 (TNFR superfamily member 4), including CCR4+OX40+ monocytes, CCR4+OX40+CD56high NK cells, CCR4+OX40+CD4+ NK T cells, and CCR4+CD38+CD4+ naïve T cells. Notably, the plasma levels of CCL17 and CCL22, measured by ELISA, increased in the acute phase of gout and declined in the interval. We also found a clue that Th2-type immune responses may participate in gout pathology. Moreover, the subset of granzyme B+ (GZMB+) CD38+ NK cells is positively correlated with serum urea acid level, and another two γδT subsets, GZMB+CD161+ γδT cells and GZMB+CCR5+ γδT cells, are negatively correlated with erythrocyte sedimentation rate. In sum, gouty arthritis is not a disease simply mediated by macrophages; multiple types of immune cell may be involved in the pathogenesis of the disease. Future research needs to shift attention to other immune cell subsets, such as NK cells and T cells, which will facilitate the identification of novel therapeutic targets.

Novel Compound-Target Interactions Prediction for the Herbal Formula Hua-Yu-Qiang-Shen-Tong-Bi-Fang.

Herbal formulae have a long history in clinical medicine in Asia. While the complexity of the formulae leads to the complex compound-target interactions and the resultant multi-target therapeutic effects, it is difficult to elucidate the molecular/therapeutic mechanism of action for the many formulae. For example, the Hua-Yu-Qiang-Shen-Tong-Bi-Fang (TBF), an herbal formula of Chinese medicine, has been used for treating rheumatoid arthritis. However, the target information of a great number of compounds from the TBF formula is missing. In this study, we predicted the targets of the compounds from the TBF formula via network analysis and in silico computing. Initially, the information of the phytochemicals contained in the plants of the herbal formula was collected, and subsequently computed to their corresponding fingerprints for the sake of structural similarity calculation. Then a compound structural similarity network infused with available target information was constructed. Five local similarity indices were used and compared for their performance on predicting the potential new targets of the compounds. Finally, the Preferential Attachment Index was selected for it having an area under curve (AUC) of 0.886, which outperforms the other four algorithms in predicting the compound-target interactions. This method could provide a promising direction for identifying the compound-target interactions of herbal formulae in silico.

Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma.

BACKGROUND: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2) in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. METHODS: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα). The animal model was confirmed by the hematoxylin and eosin (H&E) method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST), alanine amino transferase (ALT), urea and creatinine were carried out. RESULTS: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS) as well as proliferating cell nuclear antigen (PCNA), recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. CONCLUSIONS: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.

Buyang Huanwu decoction facilitates neurorehabilitation through an improvement of synaptic plasticity in cerebral ischemic rats.

BACKGROUND: Loss of neural function is a critical but unsolved issue after cerebral ischemia insult. Neuronal plasticity and remodeling are crucial for recovery of neural functions after brain injury. Buyang Huanwu decoction, which is a classic formula in traditional Chinese medicine, can positively alter synaptic plasticity. This study assessed the effects of Buyang Huanwu decoction in combination with physical exercise on neuronal plasticity in cerebral ischemic rats. METHODS: Cerebral ischemic rats were administered Buyang Huanwu decoction and participated in physical exercise after the induction of a permanent middle cerebral artery occlusion. The neurobehavioral functions and infarct volumes were evaluated. The presynaptic (SYN), postsynaptic (GAP-43) and cytoskeletal (MAP-2) proteins in the coronal brain samples were evaluated by immunohistochemistry and western blot analyses. The ultrastructure of the neuronal synaptic junctions in the same region were analyzed using transmission electron microscopy. RESULTS: Combination treatment of Buyang Huanwu decoction and physical exercise ameliorated the neurobehavioral deficits (p < 0.05), significantly enhanced the expression levels of SYN, GAP-43 and MAP-2 (p < 0.05), and maintained the synaptic ultrastructure. CONCLUSIONS: Buyang Huanwu decoction facilitated neurorehabilitation following a cerebral ischemia insult through an improvement in synaptic plasticity. Graphical abstract The Buyang Huanwu decoction (BYHWD) combined with physical exercise (PE) attenuates synaptic disruption and promotes synaptic plasticity following cerebral ischemia (stroke).

Treatment of Ankylosing Spondylitis With a Bushen-Qiangdu-Zhilv Decoction: A Case Report With a 3-year Follow-up.

Context • Ankylosing spondylitis (AS) is a refractory rheumatic disease, characterized by sacroiliitis and structural damage, and over decades, it can lead to joint fusion, frequently followed by significant spinal deformity and disability. However, to date, no method has been found to be effective in relieving or blocking structural damage to joints. Objective • The study intended to show that a decoction of Bushen-Qiangdu-Zhilv (BQZ), a therapy used in traditional Chinese medicine (TCM), can provide an alternative treatment for AS patients. Design • The research team performed a case study. Setting • The study was conducted at Guangdong Provincial Hospital of TCM in Guangzhou, China. Participant • The case study involved a 33-y-old male patient with active AS who visited the research team's clinic. Intervention • The patient took the BQZ orally 2 ×/d at 30 min after breakfast and 30 min after dinner. The patient returned to the clinic for consultation monthly. The patient took 2 servings/d for 10 mo and then received continuous BQZ treatment of the maintenance dosage for a period of approximately 3 y until December 2013. The maintenance dosage of BQZ was 3 or 4 decoctions per wk. Outcome Measures • The study used a number of measurements to evaluate the outcomes of treatment: (1) disease activity-the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); (2) functional condition-the Bath Ankylosing Spondylitis Functional Index (BASFI); (3) inflammation-ratings of morning stiffness and night pain, serum C-reactive protein (CRP) concentration measured by means of particle-enhanced immunonephelometry, and erythrocyte sedimentation rate (ESR) value as detected using the Westergren method; (4) spinal mobility-the Bath Ankylosing Spondylitis Metrology Index (BASMI); and (5) global assessments by patient and physician. Results • The participant showed improvements in inflammatory symptoms and recovery from structural damage after receiving the TCM therapy for 3 y. Conclusions • The study has shown that the long-term use of BQZ not only can lead to an improvement in inflammatory symptoms and quality of life but also can help to restore function after structural damage in AS patients.

BLZF1 expression is of prognostic significance in hepatocellular carcinoma.

BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/ß-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan-Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697-0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC.

[Treatment of Refractory Rheumatoid Arthritis by Huayu Tongbi Recipe Combined Methotrexate].

OBJECTIVE: To evaluate the clinical efficacy and safety of Huayu Tongbi Recipe (HTR) combined methotrexate (MTX) in treating refractory rheumatoid arthritis (RRA). METHODS: Totally 167 RRA patients were assigned to the treatment group (73 cases) and the control group (94 cases) according to different therapeutic methods. Patients in the treatment group were treated with HTR combined MTX, while those in the control group were treated with leflunomide (LEF) combined MTX. Clinical signs and symptoms, RF, CRP, ESR, disease activity score 28 (DAS28), and safety indicators were compared between the two groups before treatment, at week 12 and 24 after treatment. The efficacy and safety indices were also evaluated. RESULTS: At week 12 after treatment the total effective rate was 82.2% (60/73 cases) in the treatment group and 79.8% (75/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). At week 24 after treatment the total effective rate was 78.1% (57/73 cases) in the treatment group and 755% (71/94 cases) in the control group, showing no statistical difference between the two groups (chi2 = 0.15, P > 0.05). There was statistical difference in the total effective rate between week 24 and week 12 in the control group (chi2 = 0.49, P < 0.05). Clinical signs and symptoms, RF, CRP, ESR, and DAS28 were significantly improved in the two groups after 12- and 24-week treatment (P < 0.01). There was no statistical difference in the improvement at week 12 after treatment between the two groups (P > 0.05). There was statistical difference in time of morning stiffness, tender joint numbers, swollen joint numbers, patient global assessment, RF, CRP, and DAS28 at week 24 after treatment between the two groups (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.01). CONCLUSION: The efficacy of HTR combined MTX was equivalent to that of LEF (10 mg per day) combined MTX, but with more stable therapeutic effects and less adverse reactions.

Glycyrrhizin suppresses lung adenocarcinoma cell growth through inhibition of thromboxane synthase.

BACKGROUND/AIMS: The effects of glycyrrhizin treatment in lung cancer remain undetermined, despite extensive studies of the anti-tumor activities of glycyrrhizin. METHODS: Lung adenocarcinoma A549 and NCI-H23 cell lines were used in this study. Cell growth was examined by MTS assays, while apoptosis and cell cycle were determined by flow cytometric analysis. Both real-time PCR and western blotting were used to examine the expression levels of thromboxane synthase (TxAS), and TxAS activity was measured using EIA detection of the biosynthesis of TxA2. TxAS was overexpressed in NCI-H23 cells by transfection with TxAS cDNA, while TxAS was inhibited by transfection with TxAS siRNA in A549 cells. For the mouse model of lung adenocarcinoma, the effects of glycyrrhizin on tumor growth were analyzed by western blot evaluation of TxAS, PTEN and survivin. TxAS activity was determined by EIA assay. RESULTS: Glycyrrhizin suppressed cell growth in A549 cells, but not in NCI-H23 cells, by induction of apoptosis. TxAS was overexpressed in A549 cells, but the TxAS levels in NCI-H23 cells were minimal. Moreover, TxAS expression and activity were suppressed by glycyrrhizin. Glycyrrhizin had no additive effects with TxAS siRNA knockdown in suppressing A549 cell growth, whereas it completely suppressed cell growth of NCI-H23 cells transfected with TxAS cDNA. These results were further confirmed by the in vivo study. CONCLUSION: Our study suggests that the anti-tumor effect of glycyrrhizin in lung adenocarcinoma is, at least in part, TxAS-dependent. Therefore, glycyrrhizin is a promising anti-cancer agent for the treatment of lung adenocarcinoma.

Tanshinone IIA induces apoptosis in fibroblast-like synoviocytes in rheumatoid arthritis via blockade of the cell cycle in the G2/M phase and a mitochondrial pathway.

Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza BUNGE, has been documented with anti-tumor, pro-apoptotic, and anti-inflammatory activities. Salvia miltiorrhiza has long been used to treat rheumatoid arthritis (RA). Apoptosis induction of RA-fibroblast-like synoviocytes (FLS) was suggested to be a potential therapeutic approach for RA. The aim of this study was to investigate whether Tan IIA promotes apoptosis in RA-affected FLS. In this study, the viability of an immortalized FLS cell line derived from RA patients was assessed by 3-(4,5-dimethylthiazol-2-yl)-5,3-carboxymethoxyphenyl-2,4-sulfophenyl-2H-tetrazolium (MTS) assay after Tan IIA treatment. Apoptosis was measured by terminal deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) assay and flow cytometry. Cell cycle was evaluated by flow cytometry. The expressions of mitochondrial apoptosis-related molecules, including Bcl-2, Bax, mitochondrial cytochrome c (Cyt-c), cytosolic Cyt-c, apoptotic protease activating factor 1 (Apaf-1), procaspase-9, procaspase-3, caspase-9, and caspase-3 were determined by Western blotting. Our data demonstrate that Tan IIA induced apoptosis of RA-FLS, blocked the cell cycle in the G2/M phase, and regulated the protein expression of Bcl-2, Bax, and Apaf-1, the release of mitochondrial Cyt-c, and the activation of caspase-9 and caspase-3. The results support the conclusion Tan IIA treatment likely induces apoptosis of RA-FLS through blockade of the cell cycle in the G2/M phase and a mitochondrial pathway. These data suggest that Tan IIA may have therapeutic potential for RA.

Anti-inflammatory activity of extracts of Bushen-Qiangdu-Zhilv decoction, a Chinese medicinal formula, in M1-polarized RAW264.7.

BACKGROUND: Bushen-Qiangdu-Zhilv Decoction (BQZ) is one of famous traditional Chinese medical formula for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remains unknown. Pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1, play an important role in AS. We therefore evaluated if BQZ could affect the expression of these cytokines. METHODS: Crude extracts were prepared and fractioned with petroleum ether (PE), ethyl acetate (EA), n-butanol (BU) and finally water (ACE). The stability of the extracts was confirmed by high-pressure liquid chromatography (HPLC) analysis. M1-polarized RAW264.7 was induced and subsequently treated with BQZ extracts. Quantitative real-time PCR experiments were performed to measure mRNA expression of TNF-α and IL-1. RESULTS: It was found that TNF-α could be significantly suppressed by ACE extracts, whereas IL-1 was dramatically inhibited by BU extracts, which was further confirmed by dose-dependent experiments. Importantly, MTS assays showed that both ACE and BU extracts had a low cytotoxicity. CONCLUSION: Altogether, our study indicates that BQZ decoction exerts anti-AS effects via its anti-inflammatory activity and may have a low side-effect. Further analysis of the extracts of BQZ decoction could lead to a discovery of some novel drugs adding to therapeutic strategy for AS patients.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

[Regulatory roles of compound danshen in the downstream path of cyclooxygenases in rheumatoid arthritis patients' synovium].

Rheumatoid arthritis (RA) belongs to Bi syndrome (arthralgia) in Chinese medicine. Till now there lacks effective therapeutic methods. Recently cyclooxygenases (COXs) inhibitors, having regulator roles for many pro-inflammatory cytokines, have been widely used in RA treatment. But due to existing cardiovascular risks, researches on targeting the downstream specific factors of COXs have been under discussion. Considering the key role of blood stasis syndrome (BSS) in the pathology of RA and the fact that thromboxane A2 (TXA2) plays a pivotal role in BSS, we theoretically explored possible regulatory roles of Compound Danshen, a representative therapy in blood activating stasis removing method in the downstream path of COXs in synovial cells of RA. We proposed a brand new research direction of RA researches.

A bibliometric analysis of worldwide cancer research using machine learning methods.

With the progress and development of computer technology, applying machine learning methods to cancer research has become an important research field. To analyze the most recent research status and trends, main research topics, topic evolutions, research collaborations, and potential directions of this research field, this study conducts a bibliometric analysis on 6206 research articles worldwide collected from PubMed between 2011 and 2021 concerning cancer research using machine learning methods. Python is used as a tool for bibliometric analysis, Gephi is used for social network analysis, and the Latent Dirichlet Allocation model is used for topic modeling. The trend analysis of articles not only reflects the innovative research at the intersection of machine learning and cancer but also demonstrates its vigorous development and increasing impacts. In terms of journals, Nature Communications is the most influential journal and Scientific Reports is the most prolific one. The United States and Harvard University have contributed the most to cancer research using machine learning methods. As for the research topic, "Support Vector Machine," "classification," and "deep learning" have been the core focuses of the research field. Findings are helpful for scholars and related practitioners to better understand the development status and trends of cancer research using machine learning methods, as well as to have a deeper understanding of research hotspots.

Corrigendum: Deep sequencing of plasma exosomal microRNA level in psoriasis vulgaris patients.

[This corrects the article DOI: 10.3389/fmed.2022.895564.].

[Corrigendum] Role of cysteine­rich angiogenic inducer 61 in fibroblast­like synovial cell proliferation and invasion in rheumatoid arthritis.

Following the publication of the above article, an interested reader drew to the authors' attention that Fig. 4A on p. 921, showing the results from cell migration assay experiments, featured a pair of duplicated data panels. After having consulted their original data, the authors have realized that Fig. 3A on the same page, showing the fluorometric images of apoptotic cells, also contained a pair of duplicated data panels. These errors in the presentation of these figures arose inadvertently as a consequence of selecting the wrong images for the 'RA NC' data panel in Fig. 3A and the NOR-FLS data panel in Fig. 5E. The revised versions of Figs. 3 and 4 are shown on the next two pages. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and also apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 11: 917­923, 2015; DOI: 10.3892/mmr.2014.2770].

Single-cell RNA transcriptomic and plasma Lipidomic reveal the potential mechanisms of a Methotrexate-based therapy against Rheumatoid Arthritis.

OBJECTIVE: To assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic profiling were performed to reveal the potential mechanisms. METHODS: Patients were enrolled in an open-label, Simon 2-stage, single-center, single-arm trial at Guangdong Provincial Hospital of Chinese Medicine. Main inclusion criteria were defined as follows: Aged 18 to 70, low to medium disease activity, fulfilled the RA classification criteria of EULAR/ACR 2010. Patients received the oral medication of MTX 10-15 mg weekly and natural product granules twice a day. Primary outcome was the American College of Rheumatology (ACR) 20% preliminary definition of improvement. Single-cell RNA sequencing(scRNA-seq) on peripheral blood mononuclear cells (PBMCs) was used to show the aberrant metabolism before and after the trial. Plasma lipidomic profiling quantified the lipid changes caused by this MTX-based therapy. Finally, post-hoc analysis on responders and non-responders were used for further analysis. RESULTS: Between October 2020 and June 2022, 46 patients received treatment, while 42 finished follow-ups. 27 of 46 (58.70%) patients achieved ACR20, and significant changes were observed in several secondary outcomes. Comparative scRNA-seq analysis before and after the treatment revealed that lipidomic metabolism was broadly downregulated. Plasma lipidomic profiling reveals that 40 lipids were observed significantly changed. Post-hoc analysis showed the lipid changes were separately linked to clinical parameters in responders and non-responders. CONCLUSION: The study reveals that the combination therapy of HQT+MTX is effective and has a certain correlation with lipid metabolism, but more rigorous study design is still needed to confirm this speculation.

In silico analysis of serum miRNA profiles in seronegative and seropositive rheumatoid arthritis patients by small RNA sequencing.

Rheumatoid arthritis (RA) is a refractory autoimmune disease, affecting about 1% of the world's population. RA is divided into seronegative RA and seropositive RA. However, biomarkers for discriminating between seronegative and seropositive RA have not been reported. In this study, we profiled serum miRNAs in seronegative RA patients (N-RA), seropositive RA patients (P-RA) and healthy controls (HC) by small RNA sequencing. Results indicated that compared with HC group, there were one up-regulated and four downregulated miRNAs in N-RA group (fold change ≥ 2 and P value < 0.05); compared with P-RA group, there were two up-regulated and four downregulated miRNAs in N-RA group; compared with HC group, there were three up-regulated and four downregulated miRNAs in P-RA group. Among them, the level of hsa-miR-362-5p in N-RA group was up-regulated compared with that in HC group and P-RA group, and the level of hsa-miR-6855-5p and hsa-miR-187-3p in P-RA group was upregulated compared with that in N-RA group and HC group. Validation by qPCR confirmed that serum hsa-miR-362-5p level was elevated in N-RA group. Subsequently, by analyzing the target genes using RNAhybrid, PITA, Miranda and TargetScan and functions of differential miRNAs utilizing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), we found that the target genes and molecular pathways regulated by miRNAs in seronegative RA and seropositive RA were roughly the same, and miRNAs in these two diseases may participate in the occurrence and development of diseases by regulating the immune system. In conclusion, this study revealed the profiles of serum miRNAs in seronegative and seropositive RA patients for the first time, providing potential biomarkers and targets for the diagnosis and treatment of seronegative and seropositive RA.

Metabolic rewiring in keratinocytes by miR-31-5p identifies therapeutic intervention for psoriasis.

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

Cigarette smoking, cyclooxygenase-2 pathway and cancer.

Cigarette smoking is a major cause of mortality and morbidity worldwide. Cyclooxygenase (COX) and its derived prostanoids, mainly including prostaglandin E2 (PGE2), thromboxane A2 (TxA2) and prostacyclin (PGI2), have well-known roles in cardiovascular disease and cancer, both of which are associated with cigarette smoking. This article is focused on the role of COX-2 pathway in smoke-related pathologies and cancer. Cigarette smoke exposure can induce COX-2 expression and activity, increase PGE2 and TxA2 release, and lead to an imbalance in PGI2 and TxA2 production in favor of the latter. It exerts pro-inflammatory effects in a PGE2-dependent manner, which contributes to carcinogenesis and tumor progression. TxA2 mediates other diverse biologic effects of cigarette smoking, such as platelet activation, cell contraction and angiogenesis, which may facilitate tumor growth and metastasis in smokers. Among cigarette smoke components, nicotine and its derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are the most potent carcinogens. COX-2 and PGE2 have been shown to play a pivotal role in many cancers associated with cigarette smoking, including cancers of lung, gastric and bladder, while the information for the role of TxA2 and PGI2 in smoke-associated cancers is limited. Recent findings from our group have revealed how NNK influences the TxA2 to promote the tumor growth. Better understanding in the above areas may help to generate new therapeutic protocols or to optimize the existing treatment strategy.