Ropinirole suppresses LPS-induced periodontal inflammation by inhibiting the NAT10 in an ac4C-dependent manner.

BACKGROUND: Periodontitis is a chronic osteolytic inflammatory disease, where anti-inflammatory intervention is critical for restricting periodontal damage and regenerating alveolar bone. Ropinirole, a dopamine D2 receptor agonist, has previously shown therapeutic potential for periodontitis but the underlying mechanism is still unclear. METHODS: Human gingival fibroblasts (HGFs) treated with LPS were considered to mimic periodontitis in vitro. The dosage of Ropinirole was selected through the cell viability of HGFs evaluation. The protective effects of Ropinirole on HGFs were evaluated by detecting cell viability, cell apoptosis, and pro-inflammatory factor levels. The molecular docking between NAT10 and Ropinirole was performed. The interaction relationship between NAT10 and KLF6 was verified by ac4C Acetylated RNA Immunoprecipitation followed by qPCR (acRIP-qPCR) and dual-luciferase reporter assay. RESULTS: Ropinirole alleviates LPS-induced damage of HGFs by promoting cell viability, inhibiting cell apoptosis and the levels of IL-1ß, IL-18, and TNF-α. Overexpression of NAT10 weakens the effects of Ropinirole on protecting HGFs. Meanwhile, NAT10-mediated ac4C RNA acetylation promotes KLF6 mRNA stability. Upregulation of KLF6 reversed the effects of NAT10 inhibition on HGFs. CONCLUSIONS: Taken together, Ropinirole protected HGFs through inhibiting the NAT10 ac4C RNA acetylation to decrease the KLF6 mRNA stability from LPS injury. The discovery of this pharmacological and molecular mechanism of Ropinirole further strengthens its therapeutic potential for periodontitis.

Three Birds with One Stone: Multifunctional TiN-MXene-Co@CNTs Network as Sulfur/Lithium Host for High-Areal-Capacity Lithium-Sulfur Batteries.

The inevitable shuttling and slow redox kinetics of lithium polysulfides (LiPSs) as well as the uncontrolled growth of Li dendrites have strongly limited the practical applications of lithium-sulfur batteries (LSBs). To address these issues, we have innovatively constructed the carbon nanotubes (CNTs) encapsulated Co nanoparticles in situ grown on TiN-MXene nanosheets, denoted as TiN-MXene-Co@CNTs, which could serve simultaneously as both sulfur/Li host to kill "three birds with one stone" to (1) efficiently capture soluble LiPSs and expedite their redox conversion, (2) accelerate nucleation/decomposition of solid Li2S, and (3) induce homogeneous Li deposition. Benefiting from the synergistic effects, the TiN-MXene-Co@CNTs/S cathode with a sulfur loading of 2.5 mg cm-2 could show a high reversible specific capacity of 1129.1 mAh g-1 after 100 cycles at 0.1 C, and ultralong cycle life over 1000 cycles at 1.0 C. More importantly, it even achieves a high areal capacity of 6.3 mAh cm-2 after 50 cycles under a sulfur loading as high as 8.9 mg cm-2 and a low E/S ratio of 5.0 µL mg-1. Besides, TiN-MXene-Co@CNTs as Li host could deliver a stable Li plating/striping behavior over 1000 h.

Nrf2 differentially regulates osteoclast and osteoblast differentiation for bone homeostasis.

Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) is a master regulator of antioxidant response and protects cells from excessive oxidative stress. Nrf2 emerges as a prospective therapeutic target for metabolic bone disorders, in which the balance between osteoblastic bone formation and osteoclastic bone resorption is disrupted. However, the molecular mechanism through which Nrf2 modulates bone homeostasis remains unclear. In this study, we compared the differences in Nrf2-mediated antioxidant response and ROS regulation in osteoblasts and osteoclasts, both in vitro and in vivo. Findings indicated a close connection between the Nrf2 expression and its related antioxidant response with osteoclasts than osteoblasts. We next pharmacologically manipulated the Nrf2-mediated antioxidant response during osteoclast or osteoblast differentiation. Nrf2 inhibition enhanced osteoclastogenesis, while its activation suppressed it. In contrast, osteogenesis decreased irrespective of whether Nrf2 was inhibited or activated. These findings highlight the distinct ways in which the Nrf2-mediated antioxidant response regulates osteoclast and osteoblast differentiation, thereby contributing to the development of Nrf2 targeted therapies for metabolic bone diseases.

Dual-Conductive CoSe2 @TiSe2 -C Heterostructures Promoting Overall Sulfur Redox Kinetics under High Sulfur Loading and Lean Electrolyte.

Although lithium-sulfur batteries (LSBs) possess a high theoretical specific capacity and energy density, the inherent problems including sluggish sulfur conversion kinetics and the shuttling of soluble lithium polysulfides (LiPSs) have severely hindered the development of LSBs. Herein, cobalt selenide (CoSe2 ) polyhedrons anchored on few-layer TiSe2 -C nanosheets derived from Ti3 C2 Tx MXenes (CoSe2 @TiSe2 -C) are reported for the first time. The dual-conductive CoSe2 @TiSe2 -C heterostructures can accelerate the conversion reaction from liquid LiPSs to solid Li2 S and promote Li2 S dissociation process through high conductivity and lowered reaction energy barriers for promoting overall sulfur redox kinetics, especially under high sulfur loadings and lean electrolyte. Electrochemical analysis and density functional theory calculation results clearly reveal the catalytic mechanisms of the CoSe2 @TiSe2 -C heterostructures from the electronic structure and atomic level. As a result, the cell with CoSe2 @TiSe2 -C interlayer maintains a superior cycling performance with 842.4 mAh g-1  and a low-capacity decay of 0.031% per cycle over 800 cycles at 1.0 C under a sulfur loading of 2.5 mg cm-2 . More encouragingly, it with a high sulfur loading of ≈7.0 mg cm-2  still harvests a high areal capacity of ≈6.25 mAh cm-2  under lean electrolyte (electrolyte/sulfur, E/S ≈ 4.5 µL mg-1 ) after 50 cycles at 0.05 C.

IL-10 Dampens an IL-17-Mediated Periodontitis-Associated Inflammatory Network.

Emerging evidence suggests comprehensive immune profiling represents a highly promising, yet insufficiently tapped approach to identify potentially prognostic signatures for periodontitis. In this report, we agnostically identified a periodontitis-associated inflammatory expression network with multiple biomarkers identified within gingival crevicular fluid samples from study participants by applying principal component analysis. We identified an IL-17-dominated trait that is associated with periodontal disease and is inversely modified by the level of IL-10. IL-10 mitigated chemokine CXCL5 and CXCL1 expressions in IL-17-stimulated peripheral blood monocytic cells and peripheral blood monocytic cell-derived macrophages. Il10-deficient mice presented more bone loss, which was associated with more Il17 and IL-17-mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the Porphyromonas gingivalis-induced experimental murine periodontitis and ligature-induced alveolar bone-loss models. The dampening effect of IL-10 on the excessive signaling of IL-17 appeared to be mediated by innate immune cells populations rather than by gingival epithelial cells, which are the major cell target for IL-17 signaling. Additionally, elevated IL-17 response in Il10-deficient mice specifically elicited an M1-skewing macrophage phenotype in the gingiva that was associated with the advanced bone loss in the ligature model. In summary, IL-17 dominated an inflammatory network characteristic of periodontitis, and IL-10 dampens this excessive IL-17-mediated periodontitis trait.

microRNA-199a-5p regulates epithelial-to-mesenchymal transition in diabetic cataract by targeting SP1 gene.

BACKGROUND: As a common ocular complication of diabetes mellitus, diabetic cataract is becoming a leading cause of visual impairment. The progression of diabetic cataract progression involves epithelial-to-mesenchymal transition (EMT), the precise role of which remains to be investigated. As microRNAs (miRNAs) are suggested to be involved in the pathogenesis of many diseases, identification of aberrantly expressed miRNAs in diabetic lens epithelial cells (LECs) and their targets may provide insights into our understanding of diabetic cataract and potential therapeutic targets. METHODS: Diabetic cataract capsules and LECs exposed to high glucose (25 mmol/L, 1-5 days) were used to mimic the model. Quantitative RT-PCR was performed to evaluate the differential expression of miRNA. Dual luciferase reporter assay was used to identify the binding target of miR-199a-5p. The expression of EMT-associated proteins was determined by immunofluorescence and Western blot analysis. RESULTS: Our results showed the differential expression of miR-9, -16, -22, -199a and -204. MiR-199a was downregulated in diabetic cataract capsule and hyperglycemia-conditioned human LECs. Specific protein 1 could be directly targeted and regulated by miR-199a in LECs and inhibit EMT in diabetic LECs. CONCLUSION: Our findings implied miR-199a could be a therapeutic target by regulating SP1 directly to affect EMT in diabetic cataract and provided novel insights into the pathogenesis of diabetic cataract.

Role of the XIST-miR-181a-COL4A1 axis in the development and progression of keratoconus.

Background: As a disorder occurs in the eyes, keratoconus (KC) is induced by the thinning of the corneal stroma. This study was designed to reveal the key long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs involved in the mechanisms of KC. Methods: Transcriptome RNA-seq data set GSE112155 was acquired from the Gene Expression Omnibus database, which contained 10 KC samples and 10 myopic control samples. Using the edgeR package, the differentially expressed (DE)-mRNAs between KC and control samples were screened. The DE-lncRNAs and DE-miRNAs in this data set were identified using the HUGO Gene Nomenclature Committee (HGNC). Using the pheatmap package, bidirectional hierarchical clustering of the DE-RNAs was conducted. Then, an enrichment analysis of the DE-mRNAs was performed using the DAVID tool. Moreover, a competitive endogenous RNA (ceRNA) regulatory network was built using the Cytoscape software. After KC-associated pathways were searched within the Comparative Toxicogenomics Database, a KC-associated ceRNA regulatory network was constructed. Results: There were 282 DE-lncRNAs (192 upregulated and 90 downregulated), 40 DE-miRNAs (29 upregulated and 11 downregulated), and 910 DE-mRNAs (554 upregulated and 356 downregulated) between the KC and control samples. A total of 34 functional terms and 9 pathways were enriched for the DE-mRNAs. In addition, 6 mRNAs (including PPARG, HLA-B, COL4A1, and COL4A2), 5 miRNAs (including miR-181a), 9 lncRNAs (including XIST), and the XIST-miR-181a-COL4A1 axis were involved in the KC-associated ceRNA regulatory network. Conclusions: PPARG, HLA-B, COL4A1, COL4A2, miR-181a, and XIST might be correlated with the development of KC. Further, the XIST-miR-181a-COL4A1 axis might be implicated in the pathogenesis of KC.

Effectiveness of remineralizing agents in the prevention and reversal of orthodontically induced white spot lesions: a systematic review and network meta-analysis.

OBJECTIVES: To compare the effectiveness of remineralizing agents in the prevention and reversal of white spot lesions (WSLs), which occur during fixed orthodontic treatment, through a systematic review and network meta-analysis. MATERIALS AND METHODS: We reviewed controlled randomized clinical trial (RCT) data querying nine databases combined with a manual search (last search date: March 10, 2020). Of 2273 identified studies, 36 RCTs were finally included. After study selection and data extraction, pair-wise and network meta-analyses were performed to analyze the effectiveness of remineralizing agents in the prevention and reversal of WSLs in the short term (≤ 3 months) and long term (> 3 months). The risk of bias was assessed based on the Cochrane guidelines. Statistical heterogeneity, inconsistencies, and cumulative ranking were also evaluated. RESULTS: In terms of WSL prevention, sodium fluoride (NaF) varnish had the highest cumulative ranking for the short-term decalcification index (99.3%); acidulated phosphate fluoride (APF) foam ranked first for long-term incidence (96.9%), followed by difluorosilane (Dfs) varnish and high-concentration fluoride toothpaste (HFT) (79.4% and 77.4%, respectively). In the reversal of WSLs, no significant difference was found among different agents or their combinations for the two available outcomes (short-term integrated fluorescence loss and short-term percentage of fluorescence loss). CONCLUSIONS: In the prevention of WSLs, APF foam showed the best remineralizing effectiveness in the long term (after debonding), followed by Dfs varnish and HFT. It is unclear whether remineralizing agents can effectively reverse WSLs based on the existing evidence. CLINICAL RELEVANCE: APF foam may be recommended as a remineralizing agent for preventing orthodontically induced WSLs. PROSPERO REGISTRATION NUMBER: CRD42019116852.

Osteoblast autophagy in glucocorticoid-induced osteoporosis.

Administration of glucocorticoids is an effective strategy for treating many inflammatory and autoimmune diseases. However, glucocorticoid treatment can have adverse effects on bone, leading to glucocorticoid-induced osteoporosis (GIO), the most common form of secondary osteoporosis. Although the pathogenesis of GIO has been studied for decades, over the past ten years the autophagy machinery has been implicated as a novel mechanism. Autophagy in osteoblasts, osteocytes, and osteoclasts plays a critical role in the maintenance of bone homeostasis. Herein, we specifically discuss how osteoblast autophagy responds to glucocorticoids and its role in the development of GIO.

NEAT1 promotes retinoblastoma progression via modulating miR-124.

The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) is reportedly involved in the initiation and progression of cancers of several types. However, the role, expression status, and the detailed mechanism of NEAT1 in retinoblastoma (RB) yet need to be unraveled. We explored the role and the mechanism of NEAT1 activity in RB. Our data show enhanced NEAT1 expression in RB-affected tissues compared with the corresponding control. Functional experiments reveal that a NEAT1 knockdown in RB cells significantly inhibits proliferation, cycle progression, and facilitates apoptosis and caspase-3 and -9 activities. Besides that, miR-124 was predicted to be a target of NEAT1 and its reduced expression, as well as the inverse correlation of NEAT1 with miR-124, was observed in RB-affected tissues. Further, luciferase and RNA immunoprecipitation (RIP) assays confirmed the interaction between NEAT1 and miR-124. Rescue experiments confirmed that the inhibition of miR-124 could reverse the effect of NEAT1 on RB cell proliferation, cycle arrest, apoptosis, and caspase-3 and -9 activities. Thus, NEAT1 promotes RB progression by sponging miR-124, providing a therapeutic target for RB.

In Vivo Antibacterial Efficacy of Nitric Oxide-Releasing Hyperbranched Polymers against Porphyromonas gingivalis.

The in vivo antibacterial activity of NO-releasing hyperbranched polymers was evaluated against Porphyromonas gingivalis, a key oral pathogen associated with periodontitis, using a murine subcutaneous chamber model. Escalating doses of NO-releasing polymers (1.5, 7.5, and 37.5 mg/kg) were administered into a P. gingivalis-infected chamber once a day for 3 days. Chamber fluids were collected on day 4, with microbiological evaluation indicating a dose-dependent bactericidal action. In particular, NO-releasing polymers at 37.5 mg/kg (1170 µg of NO/kg) achieved complete bacterial eradication (>6-log reduction in bacterial viability), demonstrating greater efficacy than amoxicillin (∼4-log reduction in bacterial viability), a commonly used antibiotic. Time-kill assays further revealed that largest dose (37.5 mg/kg; 1170 µg of NO/kg) resulted in ∼3-log killing of P. gingivalis after only a single dose. Based on these results, the potential clinical utility of NO-releasing hyperbranched polymers appears promising, particularly for oral health applications.

miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R.

A growing body of evidence suggests that microRNA-494 (miR-494) could act as tumor-suppressive or oncogenic microRNAs (miRNAs) in different types of tumors. However, the biological roles and underlying mechanisms of miR-494 remain unknown in human epithelial ovarian carcinoma (EOC). Therefore, the aims of this study were to investigate the miR-494 expression and the significance of its clinical diagnosis in patients suffering EOC and to analyze its role and underlying molecular mechanism on the carcinogenesis of EOC. Here, we found that miR-494 was significantly decreased in EOC cell lines and tissues and its expression was negatively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high pathological grade, and lymph node metastasis (all P < 0.01). Functional studies showed that overexpression of miR-494 in EOC cells could remarkably inhibit proliferation, colony formation, migration, and invasion and induce cell apoptosis, G0/G1 phase arrest. An in vivo analysis revealed that the overexpression of miR-494 suppressed tumor growth in a nude mouse xenograft model system. Bioinformatic assay and dual-luciferase assay confirmed that insulin-like growth factor 1 receptor (IGF1R) was as a direct target of miR-494 in EOC cells. Western blot assay showed that overexpression of miR-494 inhibited IGF1R expression and its downstream signal protein expression. In addition, downregulation of IGF1R has similar effects with miR-494 overexpression on EOC cells and overexpression of IGF1R effectively rescued the inhibition of overexpressed miR-494 in EOC cells. These data suggested that miR-494 functions as a tumor suppressor in EOC by targeting IGF1R.

Effect of SOST gene deletion on the progression of renal interstitial fibrosis in obstructive kidney injury.

OBJECTIVES: The role of SOST/sclerostin in mediating tissue fibrogenic response to injury/inflammation remains largely unknown. Thus, we conducted this study to determine whether SOST/sclerostin plays a role in renal interstitial fibrosis (RIF) for the first time. METHODS: Unilateral ureteral obstruction (UUO) was performed to create obstructive kidney injury model. Twelvemale SOST knockout (SOST KO) mice and 12 age-matched wild-type (WT) mice were divided into three groups: sham surgery, UUO 3 d and UUO 7 d. The mice were sacrificed at each time point and kidney tissues were collected. Histopathological changes were evaluated by hematoxylin and eosin and Masson staining, while α-smooth muscle actin (α-SMA), type I collagen (Col-I) and fibronectin (FN) expression levels were detected by RT-PCR and western-blot. RESULTS: In sham control group, neither WT nor SOST KO exhibited fibrotic change. On 3 days after UUO, total renal histopathological score and fibrotic area were aggravated and α-SMA, Col-I and FN expressions were upregulated, but no difference was observed between WT and SOST KO. On 7 days after UUO, compared with WT, SOST KO mice showed higher total renal histopathological score and fibrotic area percentage, as well as a higher level of fibrogenic marker mRNA/protein expression (except for α-SMA mRNA and FN mRNA). CONCLUSION: It is supposed that SOST gene is involved in the regulation of RIF progression. In obstructive kidney injury, SOST gene deletion would probably enhance renal fibrogenic response and promote the progression of RIF. But more evidences are needed to further identify the role of SOST/sclerostin in mediating RIF progression.

Biofeedback treatment for sleep bruxism: a systematic review.

PURPOSE: The aim of this systematic review was to evaluate the efficacy of any biofeedback treatment on sleep bruxism. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ISI Web of Science, System for Information on Grey Literature in Europe, Chinese Biomedical Literature Database, and PsycINFO up to October 2012 for randomized controlled trials and controlled clinical trials involving biofeedback treatment for sleep bruxism. Reference lists of relevant studies were hand searched. Quality assessment and data extraction were performed by two reviewers independently. RESULTS: Seven eligible studies involving 240 participants were finally included. Three of them had moderate risk of bias, and four had high risk of bias. In an electromyographic-measured sleep bruxism episode, meta-analysis showed no significant difference between contingent electrical stimulation and blank control (95% confidence interval = -12.33, 3.38, P = 0.26). Moreover, five studies reported electromyographic activity index. Due to the diversity of biofeedback modalities (auditory, electrical, and visual stimulus) and controls (splint, occlusal adjustment, etc.), these data were unable to be pooled, so only qualitative description was provided. CONCLUSIONS: In the current stage, there is no powerful evidence to support the use of biofeedback technology on sleep bruxism treatment. Contingent electrical stimulation which is defined as a kind of biofeedback modality shows no effect on reducing sleep bruxism episode compared with the no-treatment group. Although many studies support the efficacy of biofeedback treatment, more large sample-sized randomized controlled trials which adopt uniform outcome index are necessitated to verify its application.

A case of early-onset periodontitis with vitamin D deficiency: A case report and literature review.

RATIONALE: Periodontitis is an inflammatory disease with multifactorial etiology. Vitamin D, a fat-soluble vitamin, has protective effects on inflammatory response in various systemic conditions. The clinical features of vitamin D deficiency include growth failure, hypotonia, pathologic fractures, rachitic rosary, tetany and so on. Here we present a case of 12-year-old girl affected by early-onset periodontitis accompanied with vitamin D deficiency. PATIENT CONCERNS: A 12-year-old girl with gingival redness, bleeding associated with tooth brushing, and mandibular anterior teeth movement, with difficulty in mastication for the past 2 months. There is no relevant family history or special systemic disease history. The serological microelement test showed vitamin D levels were significantly lower than normal range. Immunological test showed abnormal CD4+/CD8+(CD3+CD4+/CD3+CD8+) ratio as well. DIAGNOSES: Based on the clinical and serological findings, this patient was ultimately diagnosed with early-onset periodontitis accompanied with vitamin D deficiency. INTERVENTIONS: The main treatments for this patient were 3-fold: periodontal therapy, vitamin D supplement and oral hygiene instructions. OUTCOMES: Following 1-year therapy, periodontal conditions recovered and became stable. And serological vitamin D levels returned to normal range. LESSONS: The case of interest serves as an important reminder to clinicians, that the early-onset periodontitis may be associated with micronutrients abnormalities, and early-diagnosis and treatment could avoid the body heathy disorders.

Ferroptosis-related genes LPCAT3 and PGD are potential diagnostic biomarkers for osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common chronic joint disease and how ferroptosis contributes to OA has garnered much attention recently. Bioinformatics promoted the discovery of ferroptosis-related biomarkers for OA. But since OA is a whole-joint disease, sensitive biomarkers for OA are still limited. We herein focused on subchondral bone, a joint component often-ignored by existing bioinformatic reports, to identify ferroptosis-related diagnostic biomarkers for OA. METHOD: Microarray datasets GSE51588 and GSE55457 were downloaded from Gene Expression Omnibus database. Ferroptosis-related differential expression genes (Ferr-DEGs) between OA and normal samples were identified and their functional enrichment was analyzed. Common genes for OA diagnosis were selected from Ferr-DEGs using the combination of SVM-RFE, LASSO regression, and RandomForest machine learning algorithms. Common genes' diagnostic value was verified by receiver operating characteristic (ROC) curve and their association with immune infiltration was analyzed by CIBERSORT. Finally, candidate gene's expression was verified in chondrocytes from OA patients and in an in vitro IL-1ß-induced OA model, by RT-PCR. RESULTS: Two ferroptosis-related genes, LPCAT3 and PGD, were identified as OA diagnostic biomarkers and confirmed by ROC diagnostic test. The association of LPCAT3 and PGD with the infiltration of several types of immune cells was identified. The decreased expression of LPCAT3 and PGD was both confirmed in OA chondrocytes and IL-1ß-induced OA condition. CONCLUSIONS: We identified ferroptosis-related genes LPCAT3 and PGD as potential diagnostic biomarkers for OA, which may offer insight into the role of ferroptosis in OA and provides useful information for the diagnosis and treatment of OA.

Recent developments and perspectives of MXene-Based heterostructures in photocatalysis.

Energy crises and environmental degradation are serious in recent years. Inexhaustible solar energy can be used for photocatalytic hydrogen production or CO2 reduction to reduce CO2 emissions. At present, the development of efficient photocatalysts is imminent. MXene as new two-dimensional (2D) layered material, has been used in various fields in recent years. Based on its high conductivity, adjustable band gap structure and sizable specific surface area, the MXene is beneficial to hasten the separation and reduce the combination of photoelectron-hole pairs in photocatalysis. Nevertheless, the re-stacking of layers because of the strong van der Waals force and hydrogen bonding interactions seriously hinder the development of MXene material as photocatalysts. By contrast, the MXene-based heterostructures composed of MXene nanosheets and other materials not only effectively suppress the re-stacking of layers, but also show the superior synergistic effects in photocatalysis. Herein, the recent progress of the MXene-based heterostructures as photocatalysts in energy and environment fields is summarized in this review. Particularly, new synthetic strategies, morphologies, structures, and mechanisms of MXene-based heterostructures are highlighted in hydrogen production, CO2 reduction, and pollutant degradation. In addition, the structure-activity relationship between the synthesis strategy, components, morphology and structure of MXene-based heterostructures, and their photocatalytic properties are elaborated in detail. Finally, a summary and the perspectives on improving the application study of the heterostructures in photocatalysis are presented.

IL-17: Balancing Protective Immunity and Pathogenesis.

The biological role of interleukin 17 (IL-17) has been explored during recent decades and identified as a pivotal player in coordinating innate and adaptive immune responses. Notably, IL-17 functions as a double-edged sword with both destructive and protective immunological roles. While substantial progress has implicated unrestrained IL-17 in a variety of infectious diseases or autoimmune conditions, IL-17 plays an important role in protecting the host against pathogens and maintaining physiological homeostasis. In this review, we describe canonical IL-17 signaling mechanisms promoting neutrophils recruitment, antimicrobial peptide production, and maintaining the epithelium barrier integrity, as well as some noncanonical mechanisms involving IL-17 that elicit protective immunity.

Infrared Imageries of Human Body Activated by Tea Match the Hypothesis of Meridian System.

Human meridian (Jingluo) system was hypothesized by traditional Chinese medicine (TCM) for thousands of years, suggesting 12 normal meridian channels going through respective organs, carrying fluid and energy, and laying thermal effects. Some treatments based on meridians have been proved effective. However, existence of meridians has never been confirmed, let alone the lack of measurement for meridian phenotypes. Thermal effect is one of the major phenotypes of meridian metabolism. Infrared photograph was employed to display the picture of meridians since 1970. Unfortunately, no satisfactory results have been obtained. It is possible that only when a certain meridian is activated will there be thermal effect for successful infrared photograph. In this study, 13 types of tea were selected out of the herbs to activate the hypothesized 12 meridians for imagery taking. Forty-two volunteers took part in the experiment lasted for 13 days. Different tea was tested in different day. Infrared imageries of the human bodies were taken immediately after each tea was drunk. The highest temperatures of the fingers, palms, and above the organs were derived from the imageries and analyzed. The temperatures of the organs and fingers possibly connected by 12 hypothesized meridians rose together significantly following the meridian hypothesis. Infrared imageries showed quite clear shapes of the organs activated by different kinds of tea, e.g., heart and kidneys by yellow tea, etc. Some high temperature lines also matched the hypothetic meridians. Our work displayed the probable imageries of all the 12 hypothetic meridians for the first time, and proved with data that different foods may activate different organs following the meridian hypothesis, shedding light on a possible new method of targeted drug designs. Measurements of meridian phenotypes can be developed based on this method of activation. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00090-x.

Optineurin regulates NRF2-mediated antioxidant response in a mouse model of Paget's disease of bone.

Degenerative diseases affecting the nervous and skeletal systems affect the health of millions of elderly people. Optineurin (OPTN) has been associated with numerous neurodegenerative diseases and Paget's disease of bone (PDB), a degenerative bone disease initiated by hyperactive osteoclastogenesis. In this study, we found age-related increase in OPTN and nuclear factor E2-related factor 2 (NRF2) in vivo. At the molecular level, OPTN could directly interact with both NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) for up-regulating antioxidant response. At the cellular level, deletion of OPTN resulted in increased intracellular reactive oxygen species and increased osteoclastogenic potential. At the tissue level, deletion of OPTN resulted in substantially increased oxidative stress derived from leukocytes that further stimulate osteoclastogenesis. Last, curcumin attenuated hyperactive osteoclastogenesis induced by OPTN deficiency in aged mice. Collectively, our findings reveal an OPTN-NRF2 axis maintaining bone homeostasis and suggest that antioxidants have therapeutic potential for PDB.