Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.

Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD.

Oxymatrine protects articular chondrocytes from IL-1ß-induced damage through autophagy activation via AKT/mTOR signaling pathway inhibition.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1ß (IL-1ß)-induced damage and the potential mechanisms of action. METHODS: Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1ß stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. RESULTS: OMT alleviated IL-1ß-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1ß treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1ß treatment was limited when autophagy was inhibited by 3-MA. CONCLUSIONS: OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1ß-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.

Validation of the IMPEDE VTE score for prediction of venous thromboembolism in Chinese patients with multiple myeloma: A single-center retrospective cohort study.

Multiple myeloma (MM) significantly increases the risk of venous thromboembolism (VTE) within 6 months of treatment initiation. The IMPEDE VTE score is a VTE risk prediction model which is recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines, but it lacks validation among Asians, including Chinese MM patients. We performed a retrospective chart review of 405 Chinese with newly diagnosed MM who started therapy at Beijing Jishuitan Hospital between April 2013 to October 2022. The 6-month cumulative incidence of VTE was 3.8 % (95 % CI:1.6-7.6), 8.6 % (95 % CI: 5.3-21.9) and 40.5 % (95 % CI: 24.9-55.7) in the low-, intermediate- and high-risk groups (P < 0.001), respectively. The C-statistic of the IMPEDE VTE scores for predicting VTE within 6 months of treatment initiation was 0.74 (95 % CI: 0.65-0.83). Of note, in this single-center cohort study, we propose that the anticoagulant LMWH may be more effective than the antiplatelet aspirin in potentially preventing VTE in newly diagnosed MM patients. Our findings suggest that the IMPEDE VTE score is a valid evidence-based risk stratification tool in Chinese patients with newly diagnosed MM.

Effect of Glycine on the Wet Carbonation of Steel Slag Used as a Cementitious Material.

The wet carbonation process of steel slag (SS) is envisaged to be an effective way to sequestrate CO2 and improve the properties of SS as a supplementary cementitious material. However, the carbonation process still struggles with having a low carbonation efficiency. This paper studied the effect of glycine on the accelerated carbonation of SS. The phase composition change of carbonated SS was analyzed via XRD, FT-IR, and TG-DTG. The carbonation process of SS is facilitated by the assistance of glycine, with which the carbonation degree is increased. After 60 min of carbonation, SS with glycine obtained a CO2 sequestration rate of 9.42%. Meanwhile, the carbonation reaction could decrease the content of free calcium oxide in SS. This significantly improves the soundness of SS-cement cementitious material, and the compressive strength of cementitious materials that contain carbonated SS with glycine is improved. Additionally, the cycling performance of glycine in the successive wet carbonation process of SS was investigated. Multicycle experiments via solvent recovery demonstrated that although the promotion effect of glycine was reduced after each cycle, compared with the SS-water system, the carbonation process could still be facilitated, demonstrating that successive wet carbonation via solvent recovery has considerable potential. Herein, we provide a new idea to facilitate the wet carbonation process of SS and improve the properties of SS-cement cementitious material.

Comparative pharmacokinetics of 11 major bioactive components between two dosage forms of Qixue Shuangbu Prescription in rats by ultra-high-performance liquid chromatography-tandem mass spectrometry.

Although Qixue Shuangbu Prescription (QSP) is a classic Chinese medicine prescription for treating chronic heart failure. Low bioavailability due to the insolubility and poor biofilm permeability of the main bioactive ingredients of QSP is still a key factor limiting its efficacy. In this study, a novel self-microemulsifying drug delivery system was proposed to effectively improve the bioavailability of QSP. The qualified ultra-high-performance liquid chromatography-tandem mass spectrometry methodology was established to investigate the pharmacokinetics characteristics of the QSP self-microemulsifying drug delivery system. Our results showed that 11 components in the self-microemulsifying drug delivery system group had prolonged T1/2 and MRT0-t values compared with QSP extract. The Cmax of calycosin-7-glucoside (CG), vanillic acid and paeoniflorin increased 2.5 times, 2.4 times and 2.3 times, respectively. The relative bioavailability values of CG, paeoniflorin and ononin were most significantly affected, increasing by 383.2%, 336.5% and 307.1%, respectively. This study promoted the development of new dosage forms of QSP and provided a useful reference for improving dosage forms to solve the problem of low bioavailability of traditional Chinese medicine.

Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota.

Maternal dietary patterns during pregnancy have been demonstrated to impact the structure of the gut microbiota in offspring, altering their susceptibility to diseases. This study is designed to elucidate whether the impact of folic acid supplementation during pregnancy on hepatic steatosis in male offspring of rat dams exposed to a high-fat diet (HFD) is related to gut-liver axis homeostasis. In this study, female rats were administered a HFD and simultaneously supplemented with 5 mg/kg folic acid throughout their pregnancy. Histopathological examination showed that folic acid supplementation effectively ameliorated hepatic lipid accumulation and inflammatory infiltrate in male offspring subjected to a maternal HFD. Maternal folic acid supplementation reduced the abundance of Desulfobacterota and the Firmicutes/Bacteroidota (F/B) ratio in male offspring. The expression of tight junction proteins in the colon was significantly upregulated, and the serum LPS level was significantly reduced. Furthermore, there was a notable reduction in the hepatic expression of the TLR4/NF-κB signaling pathway and subsequent inflammatory mediators. Spearman's correlation analysis revealed significant associations between hepatic inflammation-related indices and several gut microbiota, particularly Desulfobacterota and Lactobacillus. With a reduction in hepatic inflammation, the expression of PPAR-α was upregulated, and the expression of SREBP-1c and its downstream lipid metabolism-related genes was downregulated. In summary, folic acid supplementation during pregnancy modulates gut microbiota and enhances intestinal barrier integrity in male offspring of HFD dams. This helps reduce the LPS leakage and suppress the expression of TLR4/NF-κB pathway in the liver, thereby improving lipid metabolism disorders, and alleviating hepatic steatosis.

Critical review on anthocyanins in blue honeysuckle (Lonicera caerulea L.) and their function.

Blue honeysuckle (Lonicera caerulea L.) is an emerging commercial fruit in the world, has been known for its multiple anthocyanins in the berries, cyanidin-3-glucoside (C3G) is a major anthocyanin in berries and it makes up 76-92% of the total anthocyanins content, with high antioxidant capacity, and widely used in food products. In this review, recent studies related to anthocyanins in blue honeysuckle were sorted out, including the current status of research on anthocyanins in blue honeysuckle berries, especially C3G, qualitative and quantitative analysis of anthocyanins in berries, extraction and purification methods of anthocyanins from blue honeysuckle, in addition, biological effects of blue honeysuckle, and recommended utilization. Blue honeysuckle contains polyphenols, flavonoids, anthocyanins, minerals, and multiple bioactive compounds, it has been extensively reported to have significant antioxidant, cardioprotective, anti-inflammatory, neuroprotective, anticancer, and anti-diabetic functions, and has been used in a variety of food products as raw materials.

Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats.

The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways.

Combined exposure to multiple metals on hypertension in NHANES under four statistical models.

Metals exposure has gained increasing attention in the hypertension prevention. However, previous studies have focused on the impacts of single or separated metals on hypertension, and the critical metals contributing to the prevalence of hypertension are still under discussion. We collected data from 5092 participants across three consecutive National Health and Nutrition Examination Survey (NHANES) circles (2011-2016). Weighted logistic regression, weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) analyses were conducted to evaluate the combined and individual effects of 15 urinary metals, as well as to identify the critical metals on the development of hypertension. In our study, the weighted prevalence of hypertension was 37.9%, and the average age was 47.42 years. Manganese, uranium and tin were found as the independent risk factors for hypertension, while barium, lead, and thallium were found to have protective effects against hypertension. Lead, barium, tungsten, uranium, and tin were determined as critical elements for the prediction of hypertension. No significant interaction relationship was detected between multiple metals. There might be potential positive combined effects of urinary metal mixture on hypertension. Tungsten, uranium, and tin were positively associated with hypertension while lead and barium were negatively associated with hypertension. The underlying mechanisms of urinary metal exposure on the risk of hypertension deserve further investigations.

Anti-lipid accumulation effects and mechanism of the extract and isolated compounds from Potentilla longifolia.

Potentilla longifolia is effective in the treatment of hepatitis as a Chinese herb. We firstly evaluated the effect of water extract of P. longifolia (WEPL) on mice with nonalcoholic fatty liver disease (NAFLD) induced by high-fat (HF) diet. The results showed that WEPL reduced HF-induced increases of the serum ALT, AST, TG and TC, and reduced lipid drops of liver tissues to a different extent compared with HF group; WEPL dose-dependently promoted the phosphorylation degrees of AMPK and ACC; WEPL decreased significantly genes expressions of SREBP1α, FAS and SCD1 and increased PPARα and CD36. Then three new (1-3) and 13 known compounds (4-16) were firstly-isolated from the 95% ethanol extract of this plant. Further experiments showed that a new compound (ganyearmcaooside C) showed the best inhibitory effect on lipid accumulation in 3 T3-L1 cells such as reducing the accumulation of oil droplets and triglyceride level, showing new drug potential for related diseases.

Association of maternity formula supplementation during pregnancy with small for gestational age birth in Chinese newborns.

OBJECTIVES: This study aimed to explore the association between maternity formula supplementation and small for gestational age (SGA) status in Chinese newborns. METHODS: Data were from a population-based cross-sectional survey conducted in Shaanxi, Northwest China between August and December 2013. A total of 27 780 women pregnant with singletons and 356 with twins were included in this survey. Information on use of maternity formulas fortified with vitamins, folic acid, pantothenic acid, calcium, iron, zinc, and docosahexaenoic acid (DHA) was collected. SGA was defined as birthweight <10th percentile of fetal growth. Generalized linear models and estimating equation models were used to estimate crude odds ratios (ORs) or adjusted ORs with 95% confidence intervals (CIs) for SGA. RESULTS: The rate of maternity formula supplementation during the entire pregnancy was 13.0% in the overall population. There was no significant association between maternal formula supplementation during pregnancy and the risk of total SGA birth (OR: 1.00; 95% CI, 0.90-1.11; P = 0.950). However, maternity formula supplementation during pregnancy was related to a lower risk of SGA for twins (OR: 0.49; 95% CI, 0.31-0.80; P = 0.004), twin A (OR: 0.50; 95% CI, 0.25-0.98; P = 0.045), and twin B (OR: 0.48; 95% CI, 0.25-0.95; P = 0.034). Furthermore, maternity formula supplementation during the first trimester was inversely associated with the risk of SGA birth of twins (OR: 0.32; 95% CI, 0.15-0.65; P = 0.002). CONCLUSIONS: No significant association was observed between maternity formula supplementation and total SGA birth. However, women supplemented with maternal formula during pregnancy, especially during the first trimester, may have a reduced risk of SGA birth of twins.

Folic acid ameliorates alcohol-induced liver injury via gut-liver axis homeostasis.

The gut-liver axis (GLA) plays an important role in the development of alcohol-induced liver injury. Alcohol consumption is typically associated with folic acid deficiency. However, no clear evidence has confirmed the effect of folic acid supplementation on alcohol-induced liver injury via GLA homeostasis. In this study, male C57BL/6J mice were given 56% (v/v) ethanol and 5.0 mg/kg folic acid daily by gavage for 10 weeks to investigate potential protective mechanisms of folic acid in alcohol-induced liver injury via GLA homeostasis. Histopathological and biochemical analyses showed that folic acid improved lipid deposition and inflammation in the liver caused by alcohol consumption and decreased the level of ALT, AST, TG, and LPS in serum. Folic acid inhibited the expression of the TLR4 signaling pathway and its downstream inflammatory mediators in the liver and upregulated the expression of ZO-1, claudin 1, and occludin in the intestine. But compared with the CON group, folic acid did not completely eliminate alcohol-induced intestine and liver injury. Furthermore, folic acid regulated alcohol-induced alterations in gut microbiota. In alcohol-exposed mice, the relative abundance of Bacteroidota was significantly increased, and the relative abundance of unclassified_Lachnospiraceae was significantly decreased. Folic acid supplementation significantly increased the relative abundance of Verrucomicrobia, Lachnospiraceae_NK4A136_group and Akkermansia, and decreased the relative abundance of Proteobacteria. The results of Spearman's correlation analysis showed that serum parameters and hepatic inflammatory cytokines were significantly correlated with several bacteria, mainly including Bacteroidota, Firmicutes, and unclassified_Lachnospiraceae. In conclusion, folic acid could ameliorate alcohol-induced liver injury in mice via GLA homeostasis to some extent, providing a new idea and method for prevention of alcohol-induced liver injury.

[Pharmacokinetic study of Polydopamine Guttate Pills loaded with active components of Sarcandrae Herba in rats].

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established for the determination of active components of Sarcandrae Herba, and applied to the pharmacokinetics study of multiple dosage forms. After SD rats were administered by gavage with three dosage forms [Sarcandrae Herba extract, commercial Sarcandrae Herba Guttate Pills, and polydopamine guttate pills loaded with active components of Sarcandrae Herba(PDA-Sg Guttate Pills)], blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC C_(18) column(2.1 mm×100 mm, 1.7 µm). The mobile phase consisted of water containing 0.2% formic acid and acetonitrile in gradient elution. The negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 2.0. All four components could be detected in the plasma of rats in each group at each time point except the neochlorogenic acid and cryptochlorogenic acid in the Sarcandrae Herba extract group. The guttate pills group showed a significant increase in drug content at each time point. The exposure of the main components of Sarcandrae Herba in blood was effectively increased by PDA-drug loading effect in PDA-Sg Guttate Pills(The AUC_(0-24 h) of neochlorogenic acid, cryptochlorogenic acid, isaziridin and rosmarinic acid reached 2.45, 32.90, 1.54, 4.81 times that of the commercial guttate pills). This study proves the measurability of the above-mentioned multi-component in vitro-in vivo delivery process. The pharmacokinetic study has shown that PDA-Sg Guttate Pills can effectively delay the elimination time and improve the bioavailability of the four components, which can provide theoretical data for the production of the drug.

Dendrobine inhibits dopaminergic neuron apoptosis via MANF-mediated ER stress suppression in MPTP/MPP+-induced Parkinson's disease models.

BACKGROUND: Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. PURPOSE: This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. METHODS: Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. RESULTS: Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. CONCLUSION: Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.

Effects of mental health interventions among people hospitalized with COVID-19 infection: A systematic review of randomized controlled trials.

OBJECTIVE: We evaluated the effects of mental health interventions among people hospitalized with COVID-19. METHODS: We conducted a systematic review and searched 9 databases (2 Chinese-language) from December 31, 2019 to June 28, 2021. Eligible randomized controlled trials assessed interventions among hospitalized COVID-19 patients that targeted mental health symptoms. Due to the poor quality of trials, we sought to verify accuracy of trial reports including results. RESULTS: We identified 47 randomized controlled trials from China (N = 42), Iran (N = 4) and Turkey (N = 1) of which 21 tested the efficacy of psychological interventions, 5 physical and breathing exercises, and 21 a combination of interventions. Trial information could only be verified for 3 trials of psychological interventions (cognitive behavioral, guided imagery, multicomponent online), and these were the only trials with low risk of bias on at least 4 of 7 domains. Results could not be pooled or interpreted with confidence due to the degree of poor reporting and trial quality, the frequency of what were deemed implausibly large effects, and heterogeneity. CONCLUSION: Trials of interventions to address mental health in hospitalized COVID-19 patients, collectively, are not of sufficient quality to inform practice. Health care providers should refer to existing expert recommendations and standard hospital-based practices. REGISTRATION: PROSPERO (CRD42020179703); registered on April 17, 2020.

ADAPTOR PROTEIN-1 complex-mediated post-Golgi trafficking is critical for pollen wall development in Arabidopsis.

Primexine deposition is essential for the formation of pollen wall patterns and is precisely regulated by the tapetum and microspores. While tapetum- and/or microspore-localized proteins are required for primexine biosynthesis, how their trafficking is established and controlled is poorly understood. In Arabidopsis thaliana, AP1σ1 and AP1σ2, two genes encoding the σ subunit of the trans-Golgi network/early endosome (TGN/EE)-localized ADAPTOR PROTEIN-1 complex (AP-1), are partially redundant for plant viability, and the loss of AP1σ1 function reduces male fertility due to defective primexine formation. Here, we investigated the role of AP-1 in pollen wall formation. The deposition of Acyl-CoA SYNTHETASE5 (ACOS5) and type III LIPID TRANSFER PROTEINs (LTPs) secreted from the anther tapetum, which are involved in exine formation, were impaired in ap1σ1 mutants. In addition, the microspore plasma membrane (PM) protein RUPTURED POLLEN GRAIN1 (RPG1), which regulates primexine deposition, accumulated abnormally at the TGN/EE in ap1σ1 mutants. We show that AP-1µ recognizes the YXXΦ motif of RPG1, thereby regulating its PM abundance through endocytic trafficking, and that loss of AP1σ1 decreases the levels of other AP-1 subunits at the TGN/EE. Our observations show that AP-1-mediated post-Golgi trafficking plays a vital role in pollen wall development by regulating protein transport in tapetal cells and microspores.

Ligustrazine alleviates psoriasis-like inflammation through inhibiting TRAF6/c-JUN/NFκB signaling pathway in keratinocyte.

Ligusticum chuanxiong Hort (Ligusticum; Apiaceae) (accepted name, Ligusticum striatum DC, on "The Plant List" for the latest version) is a Chinese herbal medicine (CHM) which mainly distributed in Sichuan Basin, China. Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort. Ligustrazine, also known as tetramethylpyrazine (TMP), is a main active fraction of chuanxiong. The aim of this study was to clarify the underlying mechanisms by which TMP protect against psoriasis-like inflammation in keratinocytes. Here, we demonstrated that TMP alleviated the severity and PASI scores of IMQ-induced psoriasis-like skin lesion in vivo. For the histopathology level, TMP inhibited the over-proliferation of keratinocytes in the epidermis and the substantial immune cells influx in dermis. For the mechanism of the ability of TMP on regulating inflammation, we confirmed that TMP regulate the TRAF6/c-JUN/NFκB signaling pathway through analyzing the proteomics profiling and verifying the expression of TRAF6, pho-c-Jun, pho-NFκB, so that the downstream psoriasis-relevant genes transcribed by c-JUN or NFκB were down-regulated. Furthermore, we predicted TRAF6 as the potential binding point of TMP. Accordingly, our study demonstrated that TMP regulated psoriasis-like inflammation through inhibiting TRAF6/c-JUN/NFκB signaling pathway in keratinocytes, which potentially provides evidence of the mechanism of TMP in the treatment and prevention of psoriasis.

Effects of COVID-19 Mental Health Interventions Among Children, Adolescents, and Adults Not Quarantined or Undergoing Treatment Due to COVID-19 Infection: A Systematic Review of Randomised Controlled Trials.

OBJECTIVES: Our objective was to assess the effects of mental health interventions for children, adolescents, and adults not quarantined or undergoing treatment due to COVID-19 infection. METHODS: We searched 9 databases (2 Chinese-language) from December 31, 2019, to March 22, 2021. We included randomised controlled trials of interventions to address COVID-19 mental health challenges among people not hospitalised or quarantined due to COVID-19 infection. We synthesized results descriptively due to substantial heterogeneity of populations and interventions and risk of bias concerns. RESULTS: We identified 9 eligible trials, including 3 well-conducted, well-reported trials that tested interventions designed specifically for COVID-19 mental health challenges, plus 6 other trials with high risk of bias and reporting concerns, all of which tested standard interventions (e.g., individual or group therapy, expressive writing, mindfulness recordings) minimally adapted or not specifically adapted for COVID-19. Among the 3 well-conducted and reported trials, 1 (N = 670) found that a self-guided, internet-based cognitive-behavioural intervention targeting dysfunctional COVID-19 worry significantly reduced COVID-19 anxiety (standardized mean difference [SMD] 0.74, 95% confidence interval [CI], 0.58 to 0.90) and depression symptoms (SMD 0.38, 95% CI, 0.22 to 0.55) in Swedish general population participants. A lay-delivered telephone intervention for homebound older adults in the United States (N = 240) and a peer-moderated education and support intervention for people with a rare autoimmune condition from 12 countries (N = 172) significantly improved anxiety (SMD 0.35, 95% CI, 0.09 to 0.60; SMD 0.31, 95% CI, 0.03 to 0.58) and depressive symptoms (SMD 0.31, 95% CI, 0.05 to 0.56; SMD 0.31, 95% CI, 0.07 to 0.55) 6-week post-intervention, but these were not significant immediately post-intervention. No trials in children or adolescents were identified. CONCLUSIONS: Interventions that adapt evidence-based strategies for feasible delivery may be effective to address mental health in COVID-19. More well-conducted trials, including for children and adolescents, are needed.

Combination of Photothermal Therapy with Anti-Inflammation Therapy Attenuates the Inflammation Tumor Microenvironment and Weakens Immunosuppression for Enhancement Antitumor Treatment.

Photothermal therapy has gained widespread attention in cancer treatment, although its efficacy is suppressed due to the inflammatory response and immunosuppression, resulting in a discounted therapeutic effect. In this contribution, a high-performance NIR absorption organic small chromophore is developed, which is encapsulated into Pluronic F-127 to fabricate NIR absorption organic nanoparticles (TTM NPs) with excellent photothermal conversion efficiency (51.49%) for photothermal therapy. TTM NPs based photothermal therapy are combined with Aspisol, a kind of nonsteroidal anti-inflammatory drug, to weaken the inflammation and immunosuppression tumor microenvironment and enhance the antitumor effect. The results prove that the combination therapy realizes effective thermal elimination of primary tumors, inhibition of distant tumors, and suppression of tumor metastasis. The data show that combination therapy can suppress the expression of inflammatory factors, enhance dendritic cell activation and maturation, reverse the immunosuppression, facilitate T cell infiltration, and restore antitumor cytotoxic T lymphocyte activity. This study provides a paradigm to extend the development of photothermal therapy.

Engineering Exosome-Like Nanovesicles Derived from Asparagus cochinchinensis Can Inhibit the Proliferation of Hepatocellular Carcinoma Cells with Better Safety Profile.

BACKGROUND: Exosomes are a type of membrane vesicles secreted by living cells. Recent studies suggest exosome-like nanovesicles (ELNVs) from fruits and vegetables are involved in tissue renewal process and functional regulation against inflammatory diseases or cancers. However, there are few reports on ELNVs derived from medicinal plants. METHODS: ELNVs derived from Asparagus cochinchinensis (Lour.) Merr. (ACNVs) were isolated and characterized. Cytotoxicity, antiproliferative and apoptosis-inducing capacity of ACNVs against hepatoma carcinoma cell were assessed. The endocytosis mechanism of ACNVs was evaluated on Hep G2 cells in the presence of different endocytosis inhibitors. In vivo distribution of ACNVs was detected in healthy and tumor-bearing mice after scavenger receptors (SRs) blockade. PEG engineering of ACNVs was achieved through optimizing the pharmacokinetic profiles. In vivo antitumor activity and toxicity were evaluated in Hep G2 cell xenograft model. RESULTS: ACNVs were isolated and purified using a differential centrifugation method accompanied by sucrose gradient ultracentrifugation. The optimized ACNVs had an average size of about 119 nm and showed a typical cup-shaped nanostructure containing lipids, proteins, and RNAs. ACNVs were found to possess specific antitumor cell proliferation activity associated with an apoptosis-inducing pathway. ACNVs could be internalized into tumor cells mainly via phagocytosis, but they were quickly cleared once entering the blood. Blocking the SRs or PEGylation decoration prolonged the blood circulation time and increased the accumulation of ACNVs in tumor sites. In vivo antitumor results showed that PEGylated ACNVs could significantly inhibit tumor growth without side effects. CONCLUSION: This study provides a promising functional nano platform derived from edible Asparagus cochinchinensis that can be used in antitumor therapy with negligible side effects.