Four new isocoumarins from Cajanus cajan.

Four novel new isocoumarins, cajanolactone B, C, D1 and D2 (1-4), were isolated from ethanolic extracts of the leaves of Cajanus cajan. The structural elucidation has been completed mainly depending on extensive spectroscopic analysis including UV, IR, NMR (1D and 2D), HRESIMS and chiral analysis. Notably, all these new isocoumarins were found to exist in racemic forms, among which compounds 3 and 4 share the same planar structure. This finding suggests that at least the biosynthesis of isocoumarin in C. cajan is chiral tolerant. A plausible biogenetic pathway of compounds 1-4 is proposed.

20-HETE mediated TRPV1 activation drives allokinesis via MrgprA3+ neurons in chronic dermatitis.

Rationale: Noxious stimuli are often perceived as itchy in patients with chronic dermatitis (CD); however, itch and pain mechanisms of CD are not known. Methods: TRPV1 involvement in CD was analyzed using a SADBE induced CD-like mouse model, and several loss- and gain-of-function mouse models. Trigeminal TRPV1 channel and MrgprA3+ neuron functions were analyzed by calcium imaging and whole-cell patch-clamp recordings. Lesional CD-like skin from mice were analyzed by unbiased metabolomic analysis. 20-HETE availability in human and mouse skin were determined by LC/MS and ELISA. And finally, HET0016, a selective 20-HETE synthase inhibitor, was used to evaluate if blocking skin TRPV1 activation alleviates CD-associated chronic itch or pain. Results: While normally a pain inducing chemical, capsaicin induced both itch and pain in mice with CD condition. DREADD silencing of MrgprA3+ primary sensory neurons in these mice selectively decreased capsaicin induced scratching, but not pain-related wiping behavior. In the mice with CD condition, MrgprA3+ neurons showed elevated ERK phosphorylation. Further experiments showed that MrgprA3+ neurons from MrgprA3;Braf mice, which have constitutively active BRAF in MrgprA3+ neurons, were significantly more excitable and responded more strongly to capsaicin. Importantly, capsaicin induced both itch and pain in MrgprA3;Braf mice in an MrgprA3+ neuron dependent manner. Finally, the arachidonic acid metabolite 20-HETE, which can activate TRPV1, was significantly elevated in the lesional skin of mice and patients with CD. Treatment with the selective 20-HETE synthase inhibitor HET0016 alleviated itch in mice with CD condition. Conclusion: Our results demonstrate that 20-HETE activates TRPV1 channels on sensitized MrgprA3+ neurons, and induces allokinesis in lesional CD skin. Blockade of 20-HETE synthesis or silencing of TRPV1-MrgprA3+ neuron signaling offers promising therapeutic strategies for alleviating CD-associated chronic itch.

Three new anti-inflammatory stilbenoids and a diphenyl ether derivative from Cajanus cajan.

Three new stilbenoids, namely two rare plant-derived phenanthrenes denominated Cajananthrenes A and B (1, 2) and one bibenzyl named Cajanbenzyl (3), together with a diphenyl ether derivative designated Cajanether (4), as well as five other known compounds (5-9) were isolated from the ethanolic extract of the leaves of Cajanus cajan. Their structures were determined through extensive spectroscopic analysis including UV, IR, NMR (1D and 2D) and HRESIMS as well. A plausible biogenesis pathway was proposed for the biosynthesis of compounds 1-3. Compounds 1 and 2 displayed moderate anti-inflammatory activity as evident from the inhibitory effect on NO production in LPS-stimulated RAW 264.7 macrophages with IC50 values of 73.6 and 44.6 µM respectively.

Neural Regulation of Innate Immunity in Inflammatory Skin Diseases.

As the largest barrier organ of the body, the skin is highly innervated by peripheral sensory neurons. The major function of these sensory neurons is to transmit sensations of temperature, pain, and itch to elicit protective responses. Inflammatory skin diseases are triggered by the aberrant activation of immune responses. Recently, increasing evidence has shown that the skin peripheral nervous system also acts as a regulator of immune responses, particularly innate immunity, in various skin inflammatory processes. Meanwhile, immune cells in the skin can express receptors that respond to neuropeptides/neurotransmitters, leading to crosstalk between the immune system and nervous system. Herein, we highlight recent advances of such bidirectional neuroimmune interactions in certain inflammatory skin conditions.

Access to high-performance Li-rich layered oxide cathodes via ammonium phosphate surface treatment.

Ammonium phosphate ((NH4)3PO4) has been first used as a surface treatment reagent for Li-rich cathode materials. Compared to the conventional surface treatment, the samples treated with (NH4)3PO4 exhibit an ultra-high initial Coulomb efficiency of 98.0% and excellent cycling stability. This is mainly attributed to the simultaneous construction of surface integrated structures, including oxygen vacancies, spinel phases, and Li3PO4 coating. This study demonstrates the effectiveness of ammonium phosphate surface treatment and provides a new idea for designing other cathode materials.

Translation-dependent skin hyperplasia is promoted by type 1/17 inflammation in psoriasis.

BACKGROUND: Psoriasis vulgaris (PV) is a chronic skin inflammatory disease and characterized by aberrant epidermal hyperplasia. The molecule eukaryotic initiation factor (eIF) 4E controls translation initiation of certain protein synthesis and determines cell cycle or differentiation fate. OBJECTIVE: To determine the role of eIF4E in keratinocytes abnormal differentiation in the context of psoriasis. METHODS: The expression of eIF4E in psoriatic skin lesions and normal skin from human subjects was examined by western blot and immunohistochemistry. In a murine model of psoriasis-like dermatitis that is induced by topical imiquimod, 4EGI-1 was used to inhibit eIF4E activities. To measure murine skin eIF4E and keratinocytes differentiation, immunofluorescence and western blot assays were conducted. Normal human epidermal keratinocytes (NHEK) were isolated, cultured, and stimulated with cytokines including TNF-α, IFN-γ, and IL-17A, respectively. Immunofluorescence and western blot were performed to test eIF4E and effect of 4EGI-1 in a co-culture system. RESULTS: Compared with healthy controls, skin lesions from patients with PV exhibited a higher expression of eIF4E, which was positively correlated with the epidermal thickness. This expression pattern of eIF4E was replicated by the imiquimod-induced murine model. Skin hyperplasia and eIF4E activities in the murine model were attenuated by the administration of 4EGI-1. Both IFN-γ and IL-17A, rather than TNF-α, are sufficient to induce NHEK abnormal differentiation. This effect can be disrupted by 4EGI-1. CONCLUSION: eIF4E plays a crucial role in keratinocytes abnormal differentiation driven by type 1/17 inflammation in the context of psoriasis. The initiation of abnormal translation provides an alternative treatment target for psoriasis.

Integrating lncRNAs and mRNAs Expression Profiles in Penicillin-Induced Persistent Chlamydial Infection in HeLa Cells.

Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to be associated with severe complications including ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. Nevertheless, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanisms of penicillin-induced persistent chlamydial infection.

Primary Eccrine Porocarcinoma of the Thumb With Metastasis: A Rare Case Report and Literature Review.

ABSTRACT: Eccrine porocarcinoma (EPC) is a rare malignant sweat gland tumor that accounts for approximately 0.005% of all cutaneous carcinomas. It favors the lower extremities. Only 3% of EPCs are on the hand, and only 6 cases occurring specifically on fingers have been previously documented. However, we met a patient with EPC presenting the primary lesion on the left thumb and an extensive cutaneous metastasis on the left forearm. Pathologic findings of axillary lymph nodes confirmed lymphatic metastasis.

Copper and Zirconium Codoped O3-Type Sodium Iron and Manganese Oxide as the Cobalt/Nickel-Free High-Capacity and Air-Stable Cathode for Sodium-Ion Batteries.

Considering the abundance of iron and manganese within the Earth's crust, the cathode O3-NaFe0.5Mn0.5O2 has shown great potential for large-scale energy storage. Following the strategy of introducing specific heteroelements to optimize the structural stability for energy storage, the work has obtained an O3-type NaFe0.4Mn0.49Cu0.1Zr0.01O2 that exhibits enhanced electrochemical performance and air stability. It displays an initial reversible capacity of 147.5 mAh g-1 at 0.1C between 2 and 4.1 V, a capacity retention ratio exceeding 69.6% after 100 cycles at 0.2C, and a discharge capacity of 70.8 mAh g-1 at a high rate of 5C, which is superior to that of O3-NaFe0.5Mn0.5O2. The codoping of Cu/Zr reserves the layered O3 structure and enlarges the interlayer spacing, promoting the diffusion of Na+. In addition, the structural stability and air stability observed by Cu-doping is well maintained via the incorporation of extra Zr favoring a highly reversible phase conversion process. Thus, this work has demonstrated an efficient strategy for developing cobalt/nickel-free high-capacity and air-stable cathodes for sodium-ion batteries.

Akt Phosphorylation Influences Persistent Chlamydial Infection and Chlamydia-Induced Golgi Fragmentation Without Involving Rab14.

Chlamydia trachomatis is an obligate intracellular bacterium that causes multiple diseases involving the eyes, gastrointestinal tract, and genitourinary system. Previous studies have identified that in acute chlamydial infection, C. trachomatis requires Akt pathway phosphorylation and Rab14-positive vesicles to transmit essential lipids from the Golgi apparatus in survival and replication. However, the roles that Akt phosphorylation and Rab14 play in persistent chlamydial infection remain unclear. Here, we discovered that the level of Akt phosphorylation was lower in persistent chlamydial infection, and positively correlated with the effect of activating the development of Chlamydia but did not change the infectivity and 16s rRNA gene expression. Rab14 was found to exert a limited effect on persistent infection. Akt phosphorylation might regulate Chlamydia development and Chlamydia-induced Golgi fragmentation in persistent infection without involving Rab14. Our results provide a new insight regarding the potential of synergistic repressive effects of an Akt inhibitor with antibiotics in the treatment of persistent chlamydial infection induced by penicillin.

Clinical and pathological findings of chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) is a recurrent photosensitive disease occurs predominantly in elderly men on sun-exposed areas, which seriously affect the patient's life quality. The etiology of CAD remains unknown. METHODS: Sixty-six CAD patients, 66 atopic dermatitis (AD) patients, and 46 healthy people were enrolled into this study. Patient-level data were obtained from the electronic medical record and laboratory databases. We also obtained 29 tissue samples including 16 lichenoid lesions, 7 minimal erythematous dose (MED) analysis induced lesions, and 6 normal skin samples. Histopathologic and immunohistochemical analysis were performed. RESULTS: In the clinical characteristics, albumin was lower and uric acid was higher significantly in patients diagnosed as CAD. The infection rate of CAD patient after skin biopsy was considerably high (23.3%). The serum allergen test was prone to be negative in CAD patients. Lymphocytes were the dominate infiltrating cells in early and late CAD lesions, while more CD4+, CD8+, CD69+, and CD103 + cells were found in the late lesions. There is no difference in CD4+/CD8 + ratio and CD69+/CD103 + ratio among groups. More mast cells were observed in the early-stage lesions, and more dendritic cell was observed in the late-stage lesions. CONCLUSIONS: CAD patients have certain oxidative stress and are prone to be infected after skin biopsy. Serum allergen detection is of little significance for CAD diagnosis. Mast cells may be involved in the early process of CAD, while dendritic cells and tissue-resident memory T cell (TRM) may be related to the chronic process of the disease.

[Clinical features of idiopathic ventricular tachycardia of various types and their radiofrequency ablation therapy].

OBJECTIVE: To analyze the clinical features idiopathic ventricular tachycardia (IVT) and evaluate the effect of radiofrequency ablation therapy for their management. METHODS: An retrospective analysis was conducted in 165 IVT patients who received radiofrequency ablation therapy. IVT was classified into 3 types according to the site of origin, namely the right ventricular outflow tract (RVOT-IVT, 86 cases), left ventricular septum (LV-IVT, 75 cases), and left Valsalva sinus (4 cases). RESULTS AND CONCLUSION: RVOT-IVT was more frequent in female patients than in male patients (60 vs 26, M/F ratio of 0.43). In LV-IVT, male patients prevailed (54 vs 21, M/F ratio of 2.57), suggesting a gender difference in the incidence of IVT. IVT occurred mainly in young and middle-age patients. Most RVOT-IVT occurred in the third to fourth decade of life (mean 36-/+12 years), and LV-IVT occurred at a younger age than did RVOT-IVT (mean 26-/+15 years, P<0.01). Twelve-lead ECGs revealed left bundle branch block morphology in RVOT-IVT, and most of them presented with frequent premature ventricular contraction and/or non-sustained ventricular tachycardia. All the RVOT-IVT patients were successfully ablated by radiofrequency energy in pace mapping. LV-IVT patients with right bundle branch block morphology presented sustained ventricular tachycardia for most of the time, and 97% of the patients were successfully managed with radiofrequency ablation in activation mapping. Four IVT patients were characterized by atypical bundle branch block, an inferior axis, and an R/S ratio >1 in lead V3 or V2, and their tachycardia was ablated successfully in the left sinus of Valsalva using pace mapping. Radiofrequency ablation is currently an effective procedure for IVT management.