Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS: TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.

ArhGAP11A mediates amyloid-ß generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-ß (Aß) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aß generation and Aß oligomer (Aßo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aß generation by decreasing the expression of APP, PS1, and ß-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aßo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes. In APP/PS1 mice, specific reduction of the ArhGAP11A level in neurons significantly reduces Aß production and plaque deposition and ameliorates neuronal damage, neuroinflammation, and cognitive deficits. Moreover, Aßos enhance ArhGAP11A expression in neurons by activating E2F1, which thus forms a deleterious cycle. Our results demonstrate that ArhGAP11A may be involved in AD pathogenesis and that decreasing ArhGAP11A expression may be a promising therapeutic strategy for AD treatment.

Fc effector of anti-Aß antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model.

Passive immunotherapy is one of the most promising interventions for Alzheimer's disease (AD). However, almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models. Here, we showed that Aß-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aß, antibody, and complement. Notably, anti-Aß antibodies without Fc fragment, or with blockage of CR3 or FcγRIIb, did not exert these adverse effects. Consistently, Aß-targeting antibodies, but not their Fab fragments, significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment, whereas the memory impairments in mice were gradually rescued thereafter. Since the recovery rate of synapses in humans is much lower than that in mice, our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies. Therefore, Aß-targeting antibodies lack of Fc fragment, or with reduced Fc effector function, may not induce microglial synaptic pruning, providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

Electroacupuncture for relieving itching in atopic eczema: study protocol for a multicenter, randomized, sham-controlled trial.

Background: Atopic eczema (AE) is a common atopic inflammatory skin disease affecting 2.1-4.9% of the population in different countries. Pruritus, one of the most burdensome symptoms, is often underestimated for the problems it can cause, creating a vicious loop of itching, scratching, and lichenification. Therefore, further research into practical and safe treatments that relieve itchy symptoms and enhance skin protection is key to overcoming AE. Acupuncture, with or without electrical stimulation, is one of the most commonly used therapeutic measures to treat AE. This trial aimed to objectively evaluate the efficacy and safety of the electroacupuncture (EA) antipruritic technique in AE pruritus and obtain high-level clinical evidence for the popularization and application of EA for AE. Methods and analysis: This multicenter, single-blinded, randomized controlled trial is planned to transpire from April 15, 2023, to June 30, 2025. We will recruit 132 participants with AE (44 per group). Participants will be assigned randomly to three equal-sized groups: EA, sham electroacupuncture, and sham acupuncture. Treatment will be administered three times a week during the 2-week intervention phase. The primary outcome measure is the Visual Analog Scale, with a numeric rating scale to evaluate pruritus. Secondary outcome measures include the Eczema Area and Severity Index and Dermatology Life Quality Index. Other outcome measures include physical examination, serum IgE, and safety evaluation. The number, nature, and severity of adverse events will be carefully recorded. Trial registration: ClinicalTrials.gov, 22Y11922200. Registered 3 September 2022, https://register.clinicaltrials.gov.

Efficacy and safety of biological agents for the treatment of pediatric patients with psoriasis: A bayesian analysis of six high-quality randomized controlled trials.

Background: Biological agents have been used with extreme caution in children because of their possible adverse effects. Objectives: This study used high-quality randomized controlled trials (RCTs) to provide high-level evidence to assess the effectiveness and safety of biological agents for treating children with psoriasis. Methods: We searched PubMed, Embase, Cochrane, and Web of Science databases through October 31, 2021. We included trials reporting at least one adverse event after treatment with biological agents of patients less than 18-year-old diagnosed with psoriasis. RevMan 5.3 and Stata 15.0 software were used for meta and Bayesian analyses. Results: Six trials with 864 participants were included in the analysis. The results showed a 2.37-fold higher response rate in all biologics groups than in the control group for psoriasis area and severity index 75 (PASI75) (RR= 2.37, P-value < 0.01, 95% confidence interval [CI] [1.22, 4.62]). Compared with placebo, the PASI75 response rates of etanercept (RR= 2.82, 95% [CI] [1.10, 7.21]), ustekinumab low dose (RR= 7.45, 95%[CI] [1.25, 44.58]), and ustekinumab high dose (RR= 7.25, 95%[CI] [1.21, 43.41]) were superior. Additionally, the incidence of total adverse reactions was 1.05 times higher for biologics than for controls, indicating a good safety profile (RR= 1.05, P-value = 0.53, 95%[CI] [0.92, 1.19]). Overall, these six high-quality randomized controlled trials suggest that biologics are effective and safe for pediatric patients with psoriasis. Limitations: Inclusion of few relevant, high-quality RCTs. Conclusion: The results of this study indicate that biologics can be used to treat children with moderate-to-severe psoriasis without the risk of adverse effects. Ustekinumab showed the best efficacy and the fewest adverse effects.

Current evidence on the role of lipid lowering drugs in the treatment of psoriasis.

Background: Abnormal lipid distribution is observed in patients with psoriasis, which increases their risk for atherosclerosis. Lipid-lowering drugs have a certain curative effect in the treatment of psoriasis, but there is no relevant evidence-based medical evaluation. Objective: The purpose of this systematic evaluation was to assess the efficacy, safety, and potential mechanisms of action of lipid-lowering drugs for the treatment of psoriasis. Methods: The PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinical Trial, Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, and Wanfang Database were searched for relevant articles from inception to 31 December 2021. The RevMan 5.3 and Cochrane risk-of-bias tool were used for data analysis and risk assessment, respectively. The psoriasis area and severity index (PASI) score is the primary outcome indicator in clinical studies. Based on preclinical studies, we elucidated and mapped the action mechanisms of lipid-lowering drugs in the treatment of psoriasis. Results: The study included eight randomized controlled studies, four single-arm studies, and four in vitro studies. The results showed that lipid-lowering drugs, particularly statins, administered both orally and topically, can significantly improve psoriatic skin lesions and reduce the PASI scores [standardized mean difference, (SMD): -0.94; 95% CI: [-1.58, -0.31]; p = 0.004]. Oral statins performed best at week eight (SMD: -0.92; 95% CI: [-1.39, -0.44]; p = 0.0001). The mechanism of lipid-lowering drugs in the treatment of psoriasis may be related to the inhibition of keratinocyte proliferation, inhibition of CCL20-CCR6 interaction, and reduction in the levels of inflammatory factors. Limitations: There are few studies on lipid-lowering drugs and psoriasis, and their small sample sizes may render the evidence unconvincing. Conclusion: The present findings suggest that lipid-lowering drugs are relieving symptoms in psoriasis. Lipid-lowering drugs, particularly statins, can be used to treat psoriasis with good efficacy and few side effects.

Research Advances on Anti-Cancer Natural Products.

Malignant tumors seriously threaten people's health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development.

Evidence and Potential Mechanism of Action of Lithospermum erythrorhizon and Its Active Components for Psoriasis.

Background: Traditional Chinese medicine is effective in the treatment of psoriasis and can significantly reduce skin inflammation and psoriatic lesions with minimal side effects. Shikonin (SHI) and ß,ß-dimethylacryloyl alkannin (DMA), the main active components of Lithospermum erythrorhizon, have strong anti-inflammatory effects. This systematic review aimed to evaluate the efficacy and safety of Lithospermum erythrorhizon and its main active components and to elucidate the potential mechanisms of their action in psoriasis treatment. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journals, Wan Fang, and Chinese Biomedicine databases were systematically searched for articles published between 1 January 1970, and 31 February 2021. We included clinical and preclinical studies that examined the effects of Lithospermum erythrorhizon and its active components on psoriasis. All data were analyzed using RevMan 5.3 software. The Cochrane and SYRCLE's risk-of-bias tools were used to assess the quality of all studies. Results: Eleven clinical trials including 1024 participants and 23 preclinical studies were assessed. Meta-analysis showed that when treating patients with psoriasis, the Chinese herbal medicine (CHM) formulas with Lithospermum erythrorhizon as the sovereign herb can significantly improve psoriatic dermatitis, which can significantly reduce the psoriasis area and severity index (PASI) score (mean difference [MD] = -2.00, 95% confidence interval [CI] [-3.19, -0.80], p = 0.001; I2 = 85%). The incidence rates of diarrhea (risk ratio = 0.21, 95% CI [0.06, 0.81], p = 0.02) were higher in the CHM formulas group than in the control group, whereas other adverse events were not significantly different between the two groups (p > 0.05). We evaluated the PASI score of mice on day 7 and found that SHI and DMA also alleviated psoriatic lesions (MD = -3.36, 95% CI [-4.67, -2.05], p < 0.00001, I2 = 94%). Furthermore, the epidermal thickness decreased more after SHI or DMA treatment than in the control group (MD = -34.42, 95%CI [-41.25, -27.59], p < 0.00001, I2 = 93%). Based on preclinical studies, we also summarized and mapped the mechanisms of SHI and DMA in the treatment of psoriasis. Conclusion: Available findings demonstrated that Lithospermum erythrorhizon combined with other conventional treatments is useful in treating psoriasis. Preclinical evidence has shown that the active components of Lithospermum erythrorhizon exhibit a potential anti-inflammatory effect, promote keratinocyte apoptosis, inhibit keratinocyte proliferation and angiogenesis, and block the cell cycle. In summary, our findings suggest that Lithospermum erythrorhizon and its active components can be used to treat psoriasis.

Research Advances on Matrine.

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.

Celastrol gel ameliorates imiquimod-induced psoriasis-like dermatitis in mice by targeting Langerhans cells.

BACKGROUND: Psoriasis is an autoimmune disease mediated by T cells. However, treatment remains a clinical challenge because of its frequent recurrence. Celastrol (Cel), the main active ingredient in Tripterygium wilfordii Hook F, is efficacious in treating autoimmune diseases such as psoriasis. OBJECTIVE: To investigate the effect and mechanism of topical Cel in imiquimod (IMQ)-induced psoriasis-like inflammation in mice. METHODS: Female C57BL/6 and Langerin-diphtheria toxin receptor (DTR) mice were divided into Vehicle group and Cel gel groups. IMQ was used induce psoriasis-like inflammation to establish the mouse model of psoriasis. Hematoxylin and eosin staining was used to observe changes in local inflammatory cells in the skin lesions. Enzyme-linked immunosorbent assay was used to detect protein expression levels. Flow cytometry was used to detect the cell number and cytokine expression. Polymerase chain reaction was used to detect cytokine gene expression. RESULTS: Cel gel targeted the Langerhans cells. In IMQ-induced psoriatic dermatitis, Cel gel reduced the secretion of interleukin (IL)- 23 by Langerhans cells, suppressed the interaction between Langerhans cells and γδT cells, and decreased the number of activated γδT cells and related IL-17 secretion, alleviating psoriasis-like inflammation. Furthermore, Cel gel demonstrated a glucocorticoid-like effect that could impede the recurrence of psoriasis. CONCLUSION: Cel gel reduces the secretion of IL-23 from LCs and inhibits the interaction between LCs and γδT cells to alleviate psoriasis. It also shows an effect similar to that of glucocorticoids, which can prevent psoriasis recurrence. These findings provide a new direction for the clinical treatment of psoriasis and contribute to the development of novel drugs.

Effectiveness of joint 3 + 1 malaria strategy along China-Myanmar cross border areas.

BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted. METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy. RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24). CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.

Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer's disease.

BACKGROUND: Tau pathology is a hallmark of Alzheimer's disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. METHODS: The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1ß and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1ß and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. RESULTS: We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. CONCLUSION: In combination with the previously reported therapeutic effects of rutin on Aß pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aß.

Co-expression of SOX2 and HR-HPV RISH predicts poor prognosis in small cell neuroendocrine carcinoma of the uterine cervix.

BACKGROUND: Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare cancer involving the human papilloma virus (HPV), and has few available treatments. The present work aimed to assess the feasibility of SOX2 and HPV statuses as predictive indicators of SCNEC prognosis. METHODS: The associations of SOX2 and/or high-risk (HR)-HPV RNA in situ hybridization (RISH) levels with clinicopathological characteristics and prognostic outcomes for 88 neuroendocrine carcinoma (NEC) cases were analyzed. RESULTS: Among these patients with SCNEC, SOX2, P16INK4A and HR-HPV RISH expression and SOX2/HR-HPV RISH co-expression were detected in 68(77.3%), 76(86.4%), 73(83.0%), and 48(54.5%), respectively. SOX2-positive and HR-HPV RISH-positive SCNEC cases were associated with poorer overall survival (OS, P = 0.0170, P = 0.0451) and disease-free survival (DFS, P = 0.0334, P = 0.0309) compared with those expressing low SOX2 and negative HR-HPV RISH. Alternatively, univariate analysis revealed that SOX2 and HR-HPV RISH expression, either separately or in combination, predicted the poor prognosis of SCNEC patients. Multivariate analysis revealed that the co-expression of SOX2 with HR-HPV RISH may be an independent factor of OS [hazard ratio = 3.597; 95% confidence interval (CI): 1.085-11.928; P = 0.036] and DFS [hazard ratio = 2.880; 95% CI: 1.199-6.919; P = 0.018] prediction in SCNEC. CONCLUSIONS: Overall, the results of the present study suggest that the co-expression of SOX2 with HR-HPV RISH in SCNEC may represent a specific subgroup exhibiting remarkably poorer prognostic outcomes compared with the expression of any one marker alone.

Construction of biomimetic silver nanoparticles in the treatment of lymphoma.

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma.

Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms.

Background: Psoriasis is an autoimmune skin disease associated with lipid metabolism. Sphingosine-1-phosphate (S1P) is a bioactive lipid that plays a key role in the development of autoimmune diseases. However, there is currently a lack of comprehensive evidence of the effectiveness of S1P on psoriasis. Objective: To assess the efficacy and possible mechanism of S1P and its signal modulators in the treatment of psoriasis-like dermatitis. Methods: Six databases were searched through May 8, 2021, for studies reporting S1P and its signal modulators. Two reviewers independently extracted information from the enrolled studies. Methodological quality was assessed using SYRCLE's risk of bias tool. RevMan 5.3 software was used to analyze the data. For clinical studies, the Psoriasis Area and Severity Index score were the main outcomes. For preclinical studies, we clarified the role of S1P and its regulators in psoriasis in terms of phenotype and mechanism. Results: One randomized double-blind placebo-controlled trial and nine animal studies were included in this study. The pooled results showed that compared with control treatment, S1P receptor agonists [mean difference (MD): -6.80; 95% confidence interval (CI): -8.23 to -5.38; p<0.00001], and sphingosine kinase 2 inhibitors (MD: -0.95; 95% CI: -1.26 to -0.65; p<0.00001) alleviated psoriasis-like dermatitis in mice. The mechanism of S1P receptor agonists in treating psoriasis might be related to a decrease in the number of white blood cells, topical lymph node weight, interleukin-23 mRNA levels, and percentage of CD3+ T cells (p<0.05). Sphingosine kinase 2 inhibitors ameliorated psoriasis in mice, possibly by reducing spleen weight and cell numbers (p<0.05). Conclusions: S1P receptor agonists and sphingosine kinase 2 inhibitors could be potential methods for treating psoriasis by decreasing immune responses and inflammatory factors.

Fire Needle Therapy for the Treatment of Psoriasis: A Quantitative Evidence Synthesis.

Background: Fire needle therapy is a method of quickly piercing into acupoints with red-hot needles to treat diseases. Recently, multiple studies have reported that fire needle therapy is effective in the treatment of psoriasis; however, there are few articles systematically evaluating the effect of this therapy. Therefore, this systematic and meta-analysis study is conducted to estimate the efficacy and safety of fire needle therapy for psoriasis. Methods: PubMed, Embase, CNKI, VIP, CBM, CENTRAL, and Wan Fang databases were systematically searched from the dates of construction of these databases to August 24, 2019, and randomized controlled trials assessing patients with psoriasis who were treated with fire needle therapy alone or in combination with other drugs were also evaluated. Results: Fire needle therapy was effective in treating psoriasis (p = 0.0002; risk ratio [RR], 1.20; 95% confidence interval [CI], 1.09-1.33) with a lower recurrence rate (p = 0.005; RR, 0.48; 95% CI, 0.29-0.80). Adverse events after fire needle treatment were similar to those without fire needle treatment (p = 0.38; RR, 0.67; 95% CI, 0.28-1.63). After fire needle treatment, the number of cluster of differentiation (CD)8+T cells, type 1 helper cells, interleukin (IL)-2, and interferon (IFN)-γ decreased, whereas the number of CD4+T cells, type 2 helper cells, IL-4, IL-10, and the proportion of CD4+T cells and CD8+T cells increased. Conclusions: Fire needle therapy, specifically in combination with oral medicines, is effective in treating patients with psoriasis with low recurrence rates.

Association Between Psoriasis and Dementia: Current Evidence.

Background: Psoriasis and dementia are both inflammatory diseases. The association between psoriasis and dementia has rarely been investigated, and the existing results are conflicting. Thus, we conducted this study to evaluate whether an association exists between psoriasis and dementia. Methods: We searched for studies from six databases from inception to July 30, 2020, using subject and free words. RevMan 5.4 was used to calculate the risk ratio (RR) of dementia in the subjects with psoriasis. When heterogeneity was present, a random-effects model was used. Subgroup, sensitivity, and meta-regression analyses were performed using Stata 15.1. Results: Nine studies were identified and included in the study, of which seven that involved a total of 3,638,487 participants were included in the meta-analysis. We found that among the patients with psoriasis (RR: 1.14, 95% confidence interval [CI]: 1.06-1.24, p = 0.0009) and psoriatic arthritis (RR: 2.20, 95% CI: 1.29-3.78, p = 0.004), the proportions of those with non-vascular dementia (RR: 1.13, 95% CI: 1.11-1.15, p < 0.00001) and vascular dementia (RR: 1.41, 95% CI: 1.09-1.82, p = 0.009) were higher than that among the patients without psoriasis. Those with dementia were also more likely to develop psoriasis, and those with severe psoriasis were less likely to die from dementia (RR: 1.88, 95% CI: 0.72-4.90, p = 0.020). The meta-regression analysis did not show any significant sources of heterogeneity. Conclusions: The patients with psoriasis and psoriatic arthritis show high prevalence of different types of dementia. Based on the findings of this study, dementia may not be considered a high-risk factor of death from severe psoriasis. However, identification of this potential risk allows for early intervention, thereby reducing comorbidities and deaths.

Efficacy and safety of fire needle therapy for blood stasis syndrome of plaque psoriasis: protocol for a randomized, single-blind, multicenter clinical trial.

BACKGROUND: Fire needle therapy is a characteristic treatment in traditional Chinese medicine (TCM). An increasing number of studies have indicated that fire needle treatment for psoriasis provides satisfactory results with few side effects and a low recurrence rate. We herein describe the protocol for a multicenter, randomized, single-blind, placebo-controlled trial that will provide high-quality evidence on the efficacy and safety of fire needle therapy for plaque psoriasis. METHODS: Ninety-two patients with blood stasis syndrome (BSS) of plaque psoriasis will be enrolled and randomly assigned to receive fire needle therapy (intervention group) or fire needle control therapy (control group) once a week for 4 weeks. The Psoriasis Area and Severity Index (PASI) score will serve as the major efficacy index, while the body surface area (BSA), Physician Global Assessment (PGA) score, Dermatology Life Quality Index (DLQI) score, patient-reported quality of life (PRQoL), visual analog scale (VAS) score for itching, TCM symptom score, and relapse rate will be assessed as secondary outcomes. The PASI score, BSA, PGA score, and VAS score for itching will be evaluated at baseline and during the 4-week treatment and follow-up periods. DLQI score, PRQoL, and TCM symptom score will be assessed at baseline and during the treatment period. Recurrence will be evaluated during the follow-up period. Safety assessments include vital sign monitoring, routine blood tests, blood biochemistry, routine urine tests, pregnancy tests, physical examinations, and adverse-event recording. SAS software will be used for data analysis. The data network platform will be designed by the data management center of Nanjing Ningqi Medical Technology Co., Ltd. DISCUSSION: It is believed that fire needle therapy can activate the meridians, promote blood circulation, and regulate skin immunity. BSS of plaque psoriasis is related to not only immune dysfunction but also poor or stagnant blood flow. We anticipate that the results of the trial described in this protocol will provide strong evidence for the safety and efficacy of fire needle therapy for BSS of plaque psoriasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT03953885 . Registered on May 15, 2019. Name: Fire Needle Therapy on Plaque Psoriasis with Blood Stasis Syndrome.