Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Effectiveness of mindfulness-based interventions delivered via technology versus therapist among patients on peritoneal dialysis at an outpatient clinic in Singapore.

AIMS: This study aimed to (i) evaluate the effectiveness of mindfulness-based interventions in improving self-efficacy, reducing stress and anxiety among peritoneal dialysis patients, and (ii) compare the most effective method of mindfulness based interventions. METHODS: This randomized three-arm controlled trial recruited first-time peritoneal dialysis patients from the peritoneal dialysis outpatient clinic in Singapore. Patients were randomly allocated to either video-assisted mindfulness training, therapist-assisted mindfulness training or treatment-as-usual. All groups received 4.5 days of structured peritoneal dialysis training at the peritoneal dialysis centre, while video-assisted mindfulness training and therapist-assisted mindfulness training groups were taught additional mindfulness-based techniques. The perceived stress scale, self-efficacy, and anxiety (State and Trait Anxiety Inventory) were measured at baseline, 4- and 12 weeks post-randomization, using reliable and valid instruments. RESULTS: Thirty-nine patients were recruited (13 in each group). All the therapies showed a significant time trend in anxiety. Only therapist- and video-assisted mindfulness training showed a significant trend in perceived stress scale scores but not treatment-as-usual. All Intervention X Time interactions were not significant. Patients in therapist- and video-assisted mindfulness training groups had reduced perceived stress scale scores compared to treatment-as-usual at week 12. CONCLUSION: This study demonstrated the potential of mindfulness-based interventions in reducing stress among first-time PD patients.

The effect of externally applied traditional Chinese medicine in diabetic foot: A systematic review and meta-analysis of 34 RCTs.

AIM: This study aimed to investigate the clinical efficacy of externally applied Traditional Chinese Medicine (TCM) on diabetic foot. METHODS: We searched the China Knowledge Network (CNKI), Wanfang Database, PubMed and Web of Science from inception to July 31, 2022, to find all randomized control trials (RCTs) related to externally applied TCMs in diabetic foot treatment. Information about the total effective rate, healing rate, and healing time were extracted. In addition, the relative risk (RR)/odds ratio (OR) or standardized mean difference (SMD) and 95 % confidence interval (CI) were calculated. RESULTS: Finally, a total of 34 RCTs including 3758 patients were included in this meta-analysis. There were 5 articles that reported hydropathic compress with astrogalin, 14 articles that reported MEBO burn cream, 9 articles that reported compound cortex phellodendri liquid and 6 articles that reported Shengji Yuhong ointment. Compared with the basic treatment, the externally applied TCM (astrogalin, MEBO burn cream, compound cortex phellodendri liquid and Shengji Yuhong ointment) combined with basic treatment improved the total effective rate (RR = 1.31 [1.20, 1.42], P < 0.0001) and healing rate (RR = 1.84 [1.56, 2.17], P < 0.0001) and shortened the healing time (SMD = - 2.51 [- 3.39, - 1.63], P < 0.0001). CONCLUSION: Our systematic review and meta-analysis revealed that common TCM applied externally could significantly improve the clinical efficacy comparing to the basic treatment.

Corrigendum: Compound Dihuang Granule inhibits nigrostriatal pathway apoptosis in Parkinson's disease by suppressing the JNK/AP-1 pathway.

[This corrects the article DOI: 10.3389/fphar.2021.621359.].

Clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism / 中国基层医药

Objective:To investigate the clinical effects of Jiakang Pingxiao prescription combined with methiimidazole on hyperthyroidism. Methods:A total of 100 patients with hyperthyroidism admitted to Shanxian Central Hospital from February 2018 to January 2021 were included in this study. They were randomly divided into a study group and a control group, with 50 patients in each group. The control group was treated with methiimidazole, and the study group was treated with Jiakang Pingxiao prescription combined with methiimidazole. Thyroid function, serum levels of osteocalcin (OCN), β-CTx, hypersensitive C-reactive protein, and interleukin-6 (IL-6) were compared between the two groups. Results:After treatment, serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) in the study group were (3.10 ± 1.36) mU/L, (5.76 ± 1.25) pmol/L, (15.22 ± 1.95) pmol/L, respectively, which were significantly lower than (4.88 ± 1.47) mU/L, (7.13 ± 1.32) pmol/L, (19.07 ± 2.02) pmol/L in the control group ( t = 5.27, 4.71, 6.29, all P < 0.05). Serum OCN, β-CTx, hS-CRP, and IL-6 in the study group were (17.36 ± 2.62) μg/L, (0.32 ± 0.04) μg/L, (4.07 ± 0.86) mg/L, and (1.38 ± 0.21) pg/L, respectively, which were significantly lower than (26.05 ± 2.88) μg/L, (0.51 ± 0.09) μg/L, (6.23 ± 0.91) mg/L, (1.89 ± 0.28) pg/L in the control group ( t = 12.37, 10.40, 7.39, 8.57, all P < 0.05). The incidence of adverse reactions in the study group was significantly lower than that in the control group [6.00% (3/50) vs. 12.00% (3/50), χ2 = 14.78, P < 0.05). Conclusion:Jikang Pingxiao prescription combined with methiimidazole can effectively reduce the inflammatory responses in patients with hyperthyroidism, inhibit the expression of OCN and β-CTX in the serum, and improve thyroid function. The combined method is scientific and reasonable, and is suitable for clinical application. It has good therapeutic effects on hyperthyroidism and is worthy of clinical promotion.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

Correlation Between Crohn's Disease Activity and Serum Selenium Concentration.

PURPOSE: Accurate and reliable evaluation of Crohn's disease (CD) activity is crucial for monitoring and treating the disease; however, it is challenging. There is a high demand for new, reliable, and noninvasive biomarkers for estimating CD activity. Selenium deficiency is common in patients with CD; however, its correlation with disease severity remains unclear. This study aimed to assess the feasibility of using serum selenium concentration as an additional biomarker for determining the severity of CD. METHODS: This retrospective study included consecutive Asian patients aged 18 to 60 years and hospitalized for CD between May 2020 and December 2020 at the Inflammatory Bowel Disease Center (Hangzhou, China). Patients with a history of extensive small intestinal surgery and/or short bowel syndrome were excluded from analysis. Serum selenium concentration was determined using inductively coupled plasma mass spectrometry. Disease severity was evaluated based on inflammatory markers (simple endoscopic score for CD, CD activity index, Harvey-Bradshaw index, serum C-reactive protein level, erythrocyte sedimentation rate, and platelet count) and markers of nutrition status (body mass index; blood hemoglobin and hematocrit; as well as serum levels of albumin, folic acid, and vitamin D). The correlations between serum selenium level and disease severity-related parameters were analyzed using univariate and multivariate analyses. FINDINGS: The study included 94 men and 41 women. Serum selenium level was significantly and inversely associated with all tested disease activity-related parameters by univariate analysis (all, P < 0.05). Further multivariate analysis showed that the simple endoscopic score for CD and serum levels of albumin and folic acid were significantly and independently correlated with serum selenium level (all, P < 0.05). IMPLICATIONS: Serum selenium concentration was inversely correlated with endoscopic disease severity in these Asian patients with CD. It is feasible to use serum selenium level as an additional biomarker for assessing and monitoring disease activity. The present results might have been influenced by geographic region, sample size, and/or dietary factors. Serum selenium level and other indicators of CD activity measured before and after treatment may provide more useful clinical information.

Sinomenine inhibits macrophage M1 polarization by downregulating α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1.

BACKGROUND: Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis. In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. PURPOSE: To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. METHODS: The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro, α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. RESULTS: SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. CONCLUSIONS: SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro. The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.

Association between Exercise and Blood Pressure in Hypertensive Residents: A Meta-Analysis.

BACKGROUND: Exercise is recommended as an effective lifestyle behaviour for adults to prevent and treat hypertension. In this study, a randomized-effect meta-analysis was used to analyse the influence of exercise interventions on blood pressure in patients with hypertension. METHODS: Candidate papers were retrieved from PubMed, Web of Science, Embase, and Cochrane Library electronic databases, and 46 studies were finally included and analysed. RESULTS: It was shown that preplanned walking (systolic blood pressure (SBP): WMD (weighted mean difference) = -5.94, 95% CI: -8.57, -3.30; diastolic blood pressure (DBP): WMD = -2.66, 95% CI: -3.66, -1.67), yoga (SBP: WMD = -5.09, 95% CI: -9.28, -0.89; DBP: WMD = -3.06, 95% CI: -5.16, -0.96), aquatic sports (SBP WMD = -7.53, 95% CI: -11.40, -3.65; DBP: WMD = -5.35, 95% CI: -9.00, -1.69), and football (SBP: WMD = -6.06, 95% CI: -9.30, -2.82; DBP: WMD = -5.55, 95% CI: -8.98, -2.13) had significant effects on blood pressure reduction. However, Tai Chi (SBP: WMD = -8.31, 95% CI: -20.39, 3.77; DBP: WMD = -3.05, 95% CI: -6.96, 0.87) and Qigong (SBP: WMD = -4.34, 95% CI: -13.5, 4.82; DBP: WMD = -3.44, 95% CI: -7.89, 1.01) did not significantly reduce blood pressure. The heterogeneity of the meta-analysis was high. CONCLUSION: Walking, yoga, aquatic sports, and football were feasible and independent lifestyle interventions, and they were effective options for treating hypertension. More scientifically designed randomized controlled trials are needed in the future to further compare different forms of exercise for the treatment of hypertension.

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson's Disease by Suppressing the JNK/AP-1 Pathway.

Compound Dihuang Granule (CDG) is widely used in traditional Chinese medicine (TCM) for the treatment of Parkinson's disease (PD). It has been shown to alleviate PD symptoms. However, the molecular mechanisms of its action have not been established. To establish the molecular mechanisms of CDG against PD, we used TCM network pharmacology methods to predict its molecular targets and signaling pathways, followed by experimental validation. The Core Protein protein interaction (PPI) network of the 150 intersections between CDG and PD-related genes, comprising 23 proteins, including CASP3 (caspase-3), MAPK8 (JNK), FOS (c-Fos), and JUN (c-Jun). KEGG and GO analyses revealed that apoptotic regulation and MAPK signaling pathways were significantly enriched. Since c-Jun and c-Fos are AP-1 subunits, an important downstream JNK effector, we investigated if the JNK/AP-1 pathway influences CDG against apoptosis through the nigrostriatal pathways in PD rat models. Molecular docking analysis found that the top three bioactive compounds exhibiting the highest Degree Centrality following online database and LC-MS analysis had high affinities for JNK. Experimental validation analysis showed that CDG decreased the number of rotating laps and suppressed the levels of phosphorylated c-Jun, c-Fos, and JNK, as well as the number of TUNEL positive cells and the cleaved caspase-3 level in the nigrostriatal pathway. Furthermore, CDG treatment elevated the number of TH neurons, TH expression level, and Bcl-2/Bax protein ratio in a 6-OHDA-induced PD rat. These findings are in tandem with those obtained using SP600125, a specific JNK inhibitor. In conclusion, CDG suppresses the apoptosis of the nigrostriatal pathway and relieves PD symptoms by suppressing the JNK/AP-1 signaling pathway.

Complete chloroplast genome of adonis amurensis (ranunculaceae), an important cardiac folk medicinal plant in east asia.

Adonis amurensis Regel et Radde is an important cardiac folk medicinal plant which endemic to Northeast Asia. We determined the first complete chloroplast genome of A. amurensis using genome skimming approach. The cp genome was 157,032 bp long, with a large single-copy region (LSC) of 86,218 bp and a small single-copy region (SSC) of 18,212 bp separated by a pair of inverted repeats (IRs) of 26,301 bp. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. We also reconstructed the phylogeny of Adonideae and Isopyreae using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that A. amurensis is close related with Adonis sutchuenensis.

High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M

Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its β-CD inclusion compounds based on UPLC-MS/MS / 中国中药杂志

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of β-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/β-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 μm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 μL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/β-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/β-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Ginger-partitioned moxibustion plus pediatric massage for treating infantile diarrhea due to spleen deficiency: a randomized controlled clinical trial / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Methods: Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. Results: The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P<0.05). After treatment, the scores of primary and secondary symptoms decreased in all three groups, with statistically significant intra-group differences (all P<0.05); the scores of primary symptoms were significantly different between the massage plus moxibustion group and the drug group (P<0.05); the scores of secondary symptoms in the massage plus moxibustion group and the massage group were significantly different from that in the drug group (both P<0.05). The differences in the time to recover normal bowel movement frequency among the three groups were not statistically significant (P>0.05). Conclusion: Ginger-partitioned moxibustion plus pediatric massage compared with pediatric massage or smecta monotherapy shows superior clinical efficacy in treating infantile diarrhea due to spleen deficiency, and has the advantages of appetite improvement, physique strengthening and short course.

Airway relaxation mechanisms and structural basis of osthole for improving lung function in asthma.

Overuse of ß2-adrenoceptor agonist bronchodilators evokes receptor desensitization, decreased efficacy, and an increased risk of death in asthma patients. Bronchodilators that do not target ß2-adrenoceptors represent a critical unmet need for asthma management. Here, we characterize the utility of osthole, a coumarin derived from a traditional Chinese medicine, in preclinical models of asthma. In mouse precision-cut lung slices, osthole relaxed preconstricted airways, irrespective of ß2-adrenoceptor desensitization. Osthole administered in murine asthma models attenuated airway hyperresponsiveness, a hallmark of asthma. Osthole inhibited phosphodiesterase 4D (PDE4D) activity to amplify autocrine prostaglandin E2 signaling in airway smooth muscle cells that eventually triggered cAMP/PKA-dependent relaxation of airways. The crystal structure of the PDE4D complexed with osthole revealed that osthole bound to the catalytic site to prevent cAMP binding and hydrolysis. Together, our studies elucidate a specific molecular target and mechanism by which osthole induces airway relaxation. Identification of osthole binding sites on PDE4D will guide further development of bronchodilators that are not subject to tachyphylaxis and would thus avoid ß2-adrenoceptor agonist resistance.

A decade retrospective study of light/laser devices in treating nasal rosacea.

Background: Large-scale retrospective studies of light/laser in treating nasal rosacea were lacking.Objective: The study was aimed to perform a decade retrospection of the patients with nasal rosacea who were treated with light/laser devices.Methods: A study between 2008 and 2017 was performed retrospectively. Categorization of rosacea type (erythema/telangiectasia, ET; papules/pustules, PP; rhinophyma, RP) was made according to the photographs. Device settings, treatment regimens and treatment sessions of light/laser facilities were summarized. Efficacy was evaluated using a grading scale.Results: In all, 807 patients received light/laser treatments. The subtypes of nasal rosacea were ET (n = 196), PP (n = 95), RP (n = 42), ET + PP (n = 334), ET + RP (n = 15), PP + RP (n = 88), and ET + PP + RP (n = 37). The lesions of ET or PP were mainly treated with noninvasive devices (Intense pulsed light, IPL; Dye pulse light, DPL; Dual wavelength laser system, DW) and those of RP were treated with the Fractional carbon dioxide (FCO2) laser. For the mixed subtypes, the general disposal orders of lesions were ET, PP, and later RP, and the fundamental orders of devices application were IPL, DPL, DW, and FCO2 laser. For all types of rosacea except for RP (2-4 sessions), most of the patients received 4-6 sessions of treatments. Of all subtypes of ET, PP, RP, ET + PP, ET + RP, PP + RP, and ET + PP + RP, the patients who achieved more than 50% improvement accounted for 74.5%, 58.3%, 83.3%, 69.2%, 73.3%, 61.4%, and 51.4%, respectively.Conclusion: The multiple, sequential light/laser devices can be safely used in nasal rosacea with various degrees efficacies based on different types.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Feasibility of Hei Xiaoyaosan in Preventing and Treating Alzheimer's Disease Based on Theory of 'Correlation of Liver and Kidney' Based on Ca2+-CaM/CaMKⅡ-CREB Signal Pathway / 中国实验方剂学杂志

Alzheimer's disease（AD） is an incipient aging neurodegenerative disease， which increases rapidly along with the development trend of social aging and seriously threatens the health of the people. In the absence of effective preventive measures， it will have an enormous impact on the socio-economic and healthcare system. The study found that abnormal cell signal transduction is a key link in many diseases. Cell signal transduction theory has been widely used to clarify the essence of traditional Chinese medicine visceral image and the mechanism of traditional Chinese medicine. 'Correlation of Liver and Kidney' is one of the core plates of the theory of 'Correlation of Five Organs'， which is suitable for explaining the pathogenesis of complex diseases and the correlation of multiple syndromes， and guiding the prescription of clinical syndrome. Hei Xiaoyaosan， as the first choice compound for the prevention and treatment of AD based on the theory of "Correlation of Liver and Kidney' in our team， can play the effects of prevention and treatment by soothing liver and nourishing blood， strengthening spleen and tonifying kidney， and promoting brain collaterals and dredging viscerab spirit. Based on the theory of 'Correlation of Liver and Kidney'， this paper expounds the pathogenesis of AD from the perspective of traditional Chinese medicine， and puts forward the methods and ideas of the preventing and treating of AD from Ca2+-calcium/calmodulin dependent protein （CaM）/calcium/calmodulin dependent protein kinaseⅡ（CaMKⅡ）-cyclic adenosine phosphate reactive element binding protein （CREB） cell signal transduction pathway by consulting literatures and previous studies.