Recent Advances on Selenium Nutrition and Keshan Disease.

Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.

Pimpinellin ameliorates macrophage inflammation by promoting RNF146-mediated PARP1 ubiquitination.

Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.

Benefits of Monascus anka solid-state fermentation for quinoa polyphenol bioaccessibility and the anti-obesity effect linked with gut microbiota.

In our previous study, a polyphenol-utilization targeted quinoa product was developed via solid-state fermentation with Monascus anka. In this study, we investigated the polyphenol-related novel functions of the fermented product further. Compared with unfermented quinoa, M. anka fermented quinoa alleviated the trapping effect of the macromolecules, especially in the colonic fermentation stage, resulting in enhanced polyphenol bioaccessibility. Lachnoclostridium, Megasphaera, Megamonas, Dialister, and Phascolarctobacterium might contribute to polyphenol liberation and metabolism in fermented quinoa. Additionally, fermented quinoa polyphenols presented an efficient anti-obesity effect by enhancing hepatic antioxidant enzyme activities, suppressing fatty acid synthesis, accelerating fatty acid oxidation, and improving bile acid synthesis. Moreover, fermented quinoa polyphenol supplementation alleviated gut microbiota disorder induced by a high-fat diet, resulting in a decreased ratio of Firmicutes/Bacteroidota, and increased relative abundances of Lactobacillus and Lachnoclostridium. The obtained results suggested that the principal anti-obesity effect of fermented quinoa polyphenols might act through the AMPK/PPARα/CPT-1 pathway. In conclusion, M. anka solid-state fermentation effectively enhanced the bioaccessibility of quinoa, and the fermented quinoa polyphenols showed considerable anti-obesity effect. Our findings provide new perspectives for the development of dietary polyphenol-based satiety-enhancing functional foods.

Nonreciprocal magnon blockade via the Barnett effect.

We propose a scheme to achieve nonreciprocal magnon blockade via the Barnett effect in a magnon-based hybrid system. Due to the rotating yttrium iron garnet (YIG) sphere, the Barnett shift induced by the Barnett effect can be tuned from positive to negative via controlling magnetic field direction, leading to nonreciprocity. We show that a nonreciprocal unconventional magnon blockade (UMB) can emerge only from one magnetic field direction but not from the other side. Particularly, by further tuning system parameters, we simultaneously observe a nonreciprocal conventional magnon blockade (CMB) and a nonreciprocal UMB. This result achieves a switch between efficiency (UMB) and purity (CMB) of a single-magnon blockade. Interestingly, stronger UMB can be reached under stronger qubit-magnon coupling, even the strong coupling regime. Moreover, the nonreciprocity of the magnon blockade is sensitive to temperature. This work opens up a way for achieving quantum nonreciprocal magnetic devices and chiral magnon communications.

Mind In Vitro Platforms: Versatile, Scalable, Robust, and Open Solutions to Interfacing with Living Neurons.

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.

DNA Methylation Biomarkers as Prediction Tools for Therapeutic Response and Prognosis in Intermediate-Stage Hepatocellular Carcinoma.

INTRODUCTION: Alfa-fetoprotein (AFP), as the main serum tumor marker of hepatocellular carcinoma (HCC), is limited in terms of specificity and ability to predict outcomes. This study investigated the clinical utility of DNA methylation biomarkers to predict therapeutic responses and prognosis in intermediate-stage HCC. METHODS: This study enrolled 72 patients with intermediate-stage HCC who underwent locoregional therapy (LRT) between 2020 and 2021. The immediate therapeutic response and disease status during a two-year follow-up were recorded. Analysis was performed on 10 selected DNA methylation biomarkers via pyrosequencing analysis of plasma collected before and after LRT. RESULTS: Analysis was performed on 53 patients with complete responses and 19 patients with disease progression after LRT. The mean follow-up duration was 2.4 ± 0.6 years. A methylation prediction model for tumor response (MMTR) and a methylation prediction model for early progression (MMEP) were constructed. The area under the curve (AUC) for sensitivity and specificity of MMTR was 0.79 for complete response and 0.759 for overall survival. The corresponding AUCs for sensitivity and specificity of AFP and protein induced by vitamin K absence-II (PIVKA-II) were 0.717 and 0.708, respectively. Note that the MMTR index was the only significant predictor in multivariate analysis. The AUC for sensitivity and specificity of the MMEP in predicting early progression was 0.79. The corresponding AUCs for sensitivity and specificity of AFP and PIVKA-II were 0.758 and 0.714, respectively. Multivariate analysis revealed that platelet count, beyond up-to-7 criteria, and the MMEP index were strongly correlated with early tumor progression. Combining the indexes and serum markers further improved the predictive accuracy (AUC = 0.922). Multivariate analysis revealed the MMEP index was the only independent risk factor for overall survival. DISCUSSION/CONCLUSIONS: This study indicates that these methylation markers could potentially outperform current serum markers in terms of accuracy and reliability in assessing treatment response and predicting outcomes. Combining methylation markers and serum markers further improved predictive accuracy, indicating that a multi-marker approach may be more effective in clinical practice. These findings suggest that DNA methylation biomarkers may be a useful tool for managing intermediate-stage HCC patients and guiding personalized treatment, particularly for those who are at high risk for close surveillance or adjuvant treatment after LRT.

Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis.

BACKGROUND: New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT). METHODS: This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036-1.311, p = 0.011) was independent predictors of complete recanalization. The Child-Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691). CONCLUSIONS: The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.

In vitro gastrointestinal digestion of buckwheat (Fagopyrum esculentum Moench) protein: release and structural characteristics of novel bioactive peptides stimulating gut cholecystokinin secretion.

Satiety hormone cholecystokinin (CCK) plays a vital role in appetite inhibition. Its secretion is regulated by dietary components. The search for bioactive compounds that stimulate CCK secretion is currently an active area of research. The objective of this study was to evaluate the ability of buckwheat (Fagopyrum esculentum Moench) protein digest (BPD) to stimulate CCK secretion in vitro and in vivo and clarify the structural characteristics of peptides stimulating CCK secretion. BPD was prepared by an in vitro gastrointestinal digestion model. The relative molecular weight of BPD was <10 000 Da, and peptides with <3000 Da accounted for 70%. BPD was rich in essential amino acids Lys, Leu, and Val but lacked sulfur amino acids Met and Cys. It had a stimulatory effect on CCK secretion in vitro and in vivo. Chromatographic separation was performed to isolate peptide fractions involved in CCK secretion, and five novel CCK-releasing peptides including QFDLDD, PAFKEEHL, SFHFPI, IPPLFP, and RVTVQPDS were successfully identified. A sequence length range of 6-8 and marked hydrophobicity (18-28) were observed among the most CCK-releasing peptides. The present study demonstrated for the first time that BPD could stimulate CCK secretion and clarify the structural characteristics of bioactive peptides having CCK secretagogue activity in BPD.

[Role of macrophages in heart failure and traditional Chinese medicine intervention].

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

Acupuncture for gait disturbance of patients with subacute and chronic stroke: a systematic review and meta-analysis protocol.

INTRODUCTION: Hemiparetic gait is one of the most common sequelae of a stroke. Acupuncture has shown potential in correcting hemiplegic gait patterns and improving motor function recovery after stroke. However, controversial findings and a lack of supportive evidence on the effectiveness of acupuncture for post-stroke hemiplegia. The intelligent gait analysis system provides a new perspective for the study of hemiparetic gait. This systematic review aims to collect relevant studies and critically evaluate the efficacy and safety of acupuncture in alleviating gait disturbance of post-stroke hemiplegia based on quantified gait parameters. METHODS AND ANALYSIS: A comprehensive search of PubMed, Embase, Cochrane stroke group trials register, Cochrane Central Register of Controlled Trials, CINAHL, AMED, three Chinese databases (Chinese Biomedical Literatures database (CBM), National Knowledge Infrastructure (CNKI), and Wan fang Digital Periodicals), four trails registries (The WHO International Clinical Trials Registry Platform, The Chinese Clinical Trial Registry, The US National Institutes of Health Ongoing Trials Register, and The Australian New Zealand Clinical Trials Registry) will be conducted to identify randomised controlled trials of acupuncture for gait disturbance in post-stroke patients. No restrictions on language or publication status. The primary outcomes are gait temporospatial parameters (eg, step length, stride length, step width, step frequency (cadence), walking speed, etc), and gait kinematic parameters (eg, hip peak flex/extend angle, knee peak flex/extend angle, ankle peak dorsi/plantar-flexion angle, etc). We will assess bias using the approach recommended by the Cochrane Handbook for Systematic Reviews of Interventions. A meta-analysis will be conducted to synthesise the evidence for each outcome measure. The χ2 test and I2 statistic will be used for assessing heterogeneity between studies. ETHICS AND DISSEMINATION: No ethical approval is needed because no primary data is collected. Scientific conferences or peer-reviewed journals will publish the findings. PROSPERO REGISTRATION NUMBER: CRD42022384348.

A herbal product inhibits carbon tetrachloride-induced liver fibrosis by suppressing the epidermal growth factor receptor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Huayu formula (FZHY), composed of Salvia miltiorrhiza Bunge, Cordyceps sinensis, the seed of Prunus persica (L.) Batsch, the pollen of Pinus massoniana Lamb, Gynostemma pentaphyllum (Thunb.) Makino and the fruit of Schisandra chinensis (Turcz.) Baill, is a Chinese herbal compound with demonstrated clinical benefits in liver fibrosis (LF). However, its potential mechanism and molecular targets remain to be elucidated. AIM OF THE STUDY: This study was designed to evaluate the anti-fibrotic role of FZHY in hepatic fibrosis and to elucidate the potential mechanisms. MATERIALS AND METHODS: Network pharmacology was assayed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-LF. Then the core pharmaceutical target for FZHY against LF was verified by serum proteomic analysis. Further in vivo and in vitro assays were performed to verify the prediction of the pharmaceutical network. RESULTS: The network pharmacology analysis revealed that a total of 175 FZHY-LF crossover proteins were filtered into a protein-protein interaction (PPI) network complex and designated as the potential targets of FZHY against LF, and the Epidermal Growth Factor Receptor (EGFR) signaling pathway was further explored according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then analytical studies were validated by carbon tetrachloride (CCl4)-induced model in vivo. We found FZHY could attenuate CCl4-induced LF, especially decrease p-EGFR expression in α-Smooth Muscle Actin (α-SMA)-positive hepatic stellate cell (HSC) and inhibit the downstream of the EGFR signaling pathway, especially Extracellular Regulated Protein Kinases (ERK) signaling pathway in liver tissue. We further demonstrate that FZHY could inhibit Epidermal Growth Factor (EGF)-induced HSC activation, as well as the expression of p-EGFR and the key protein of the ERK signaling pathway. CONCLUSIONS: FZHY has a good effect against CCl4-induced LF. The action mechanism was associated with the down-regulation of the EGFR signaling pathway in activated HSCs.

Clinical efficacy of the shallow puncture and more-twirling acupuncture method in migraine treatment and its effects on serum 5-HT and ß-EP levels.

BACKGROUND: The incidence rate for migraine is 12% worldwide, and recurrence is common, which seriously affects the physical and mental health of patients. OBJECTIVE: To observe the clinical effect of Shallow Puncture and More Twirling method of acupuncture in treating migraine and its impact on serum 5-HT and ß-EP. METHODS: A total of 76 patients with migraine were randomized into a control group and acupuncture group with 38 cases in each. In the control group, patients were orally administered flunarizine hydrochloride before sleep, 2 capsules once daily for 4 weeks. In the acupuncture group, Shallow Puncture and More Twirling method was adopted for the acupoints of Sizhukong (SJ 23), Toulinqi (GB 15) Shuaigu (GB 8), Xuanlu (GB 5), Fengchi (GB 20), Waiguan (SJ 5), Zulinqi (GB 41). Patients were given acupuncture 3 times per week for 4 weeks. Then, the total VAS (Visual Analogue Scale) scores, composite score of migraine, serum level of 5-HT and ß-EP, and the clinical efficacy differences were observed before and after treatment and the side-effects were recorded among the two groups. RESULTS: The total VAS scores and composite score of migraine were significantly reduced among both groups after the treatment (P< 0.05), and the serum level of 5-HT and ß-EP was significantly improved (P< 0.05). Compared with control group, the acupuncture group reported lower results in VAS score and migraine composite score (P< 0.05), and higher results in serum 5-HT and ß-EP level (P< 0.05). The acupuncture group with shallow puncture and more twirling method showed a total effective rate of 86.5%, which is higher than the control group (78.4%). The difference is statistically significant (P< 0.05). CONCLUSION: Shallow Puncture and More Twirling method was superior to flunarizine hydrochloride in the treatment of clinical symptoms of migraine. Acupuncture also increases the serum level of 5-HT and ß-EP in migraine.

Efficacy of traditional Chinese exercise for obesity: A systematic review and meta-analysis.

Background: Obesity is considered one of the biggest public health problems, especially in the background of the coronavirus disease 2019 (COVID-19) lockdown. It is urgent to find interventions to control and improve it. We performed this systematic review and meta-analysis to summarize the effect of traditional Chinese exercise on obesity. Methods: We searched PubMed, Embase, Cochrane Library, the China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and WanFang database for updated articles published from the inception of each database to June 2022. Randomized controlled trials (RCTs) on traditional Chinese exercise in weight reduction were included, and related data were extracted. The random-effects model was used to adjust for the heterogeneity of the included studies, and funnel plots were used to examine publication bias. Results: A total of 701 participants were included in the 10 studies. Compared with the control group, the outcome of body weight [mean difference (MD) = -6.10; 95% CI = -8.79, -3.42], body mass index (MD = -2.03; 95% CI = -2.66, -1.41), body fat mass (MD = -3.12; 95% CI = -4.49, -1.75), waist circumference (MD = -3.46; 95% CI = -4.67, -2.24), hip circumference (MD = -2.94; 95% CI = -4.75, -1.30), and waist-to-hip ratio (MD = -0.04; 95% CI = -0.06, -0.03) in the intervention group had significant differences. Egger's test and funnel plots showed that the potential publication bias of the included studies was slight (p = 0.249). Conclusion: Traditional Chinese exercise is an effective treatment for obesity; people under the COVID-19 lockdown could do these exercises to control weight. However, a precise and comprehensive conclusion calls for RCTs on a larger scale with more rigorous designs considering the inferior methodological quality and limited retrieved articles. Systematic review registration: www.crd.york.ac.uk/PROSPERO/, identifier CRD42021270015.

Wuweixiaoduyin regulates TAZ-mediated immunoregulatory properties of Treg/TH17 cells in chronic osteomyelitis.

Wuwei xiaoduyin (WWXDY) is a prescription for Chronic osteomyelitis (COM) in traditional Chinese medicine (TCM). However, its specific mechanism remains unclear. The objective of this study was to investigate the mechanism of WWXDY in COM treatment. To clarify the potential role of TAZ in the treatment of COM by WWXDY via regulatory CD4+ T cells differentiation. The expressions of TAZ, RORγt and Foxp3 were determined by Quantitative Real-time PCR and Western blot. Besides, levels of IL-21, IL-17 and IL-10 in peripheral blood were detected by using ELISA. Molecular dynamics simulations and docking were further utilized to explore the binding mechanism. COM resulted in abnormal cell differentiation and an imbalance of Treg/Th17. In comparison with the control group, the percentage of Treg cells, Foxp3 expression and secretion of IL-17 and -21 cytokines decreased (P < 0.001), while the proportion of Th17 cells, the levels of TAZ and RORγt and concentration of IL-10 in PBMCs increased in the COM group (P < 0.001). Furthermore, the above abnormal differentiation and function of Treg/Th17 cells in COM were suppressed after treatment with WWXDY in vivo and in vitro. In addition, TEAD1 inhibited the therapeutic effect of WWXDY in terms of Treg/Th17 cells with COM. it was found that the main active ingredients were cichoric acid and isocarlinoside. WWXDY regulates immunoregulatory properties of Treg/Th17 cells in COM mainly by mediating TAZ expression. By inhibiting the chronic inflammation in COM, WWXDY is potentially used to inhibit the progression of COM into bone tumors.

A Botanical Drug Extracted From Antrodia cinnamomea: A First-in-human Phase I Study in Healthy Volunteers.

LEAC-102 is an emerging drug extracted from the medicinal fungus Antrodia cinnamomea (AC), which is traditionally used to ameliorate fatigue and liver disorders arising from excessive alcohol consumption. AC has been used as a health product with an immunomodulatory function, but its anticancer effect has not been applied in clinical therapy as a drug. This first-in-human study examined the safety and tolerability of LEAC-102 as a new drug in healthy adults.This standard 3 + 3 dose-escalation study included 18 participants administered LEAC-102 at doses of 597.6, 1195.2, 1792.8, 2390.4, or 2988 mg/day for 1 month plus 7 days of safety follow-up. The maximum planned dose was 2988 mg. Dose-limiting toxicity (DLT) was monitored from the start of LEAC-102 administration up to the final visit. The dose of LEAC-102 was escalated to the subsequent cohort as long as there was no DLT in the previous cohort. Tolerability, clinical status, safety (by laboratory parameters), and adverse event occurrence were documented weekly during the treatment and 1 week after the conclusion of the treatment.All clinical biochemistry profiles were in the normal range, and no serious adverse effects were observed. The maximum tolerated dose of LEAC-102 was determined to be 2988 mg/day because one participant experienced urticaria. Additionally, our exploratory objectives revealed that LEAC-102 significantly elevated natural killer, natural killer T, and dendritic cells in a dose-dependent manner, activated effector T cells, and upregulated programmed cell death-1 expression.The outcomes suggested that LEAC-102 was well tolerated and safe in healthy adults and exhibited potential immunomodulatory function.Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2022.2032868 .

[Common anti-inflammatory effects of heat-clearing and toxin-removing Chinese medicines on diverse cardiovascular diseases].

Cardiovascular diseases seriously affect human health and their prevalence continues to increase with the aging of the population. The integrated therapy of traditional Chinese medicine(TCM) and western medicine for cardiovascular diseases has achieved certain results, but it is still faced with new challenges. Studies have shown that inflammation plays an important role in the development of cardiovascular diseases and some of these mechanisms have common features. For example, in cardiovascular diseases, C-C motif chemokine receptor 2(CCR2)-expressing macrophages increase and promote inflammation, and excessive activation of NOD-like receptor protein 3(NLRP3) inflammasome leads to the elevation of inflammatory factors. There is also new understanding of the pathogenesis and treatment of cardiovascular diseases in TCM. The heat-toxicity theory in cardiovascular diseases and the therapeutic principle of clearing heat and removing toxin have attracted attention. The clinical and pharmacological studies on the treatment of cardiovascular diseases such as Huanglian Jiedu Decoction and Simiao Yong'an Decoction are also gradually increasing. The present study analyzed the common features of the inflammatory response mechanisms in diverse cardiovascular diseases and discussed the significance of the prevention and treatment of diverse cardiovascular diseases by the treatment method of clearing heat and removing toxin to regulate inflammation, which is expected to provide new ideas and references for clinical treatment and drug research on cardiovascular diseases with the same treatment method for different diseases.

Thermo-optically tunable slot waveguide-based dual mode-splitting resonators with enhanced sharp lineshapes.

Slot waveguide plays an essential role in achieving high-performance on-chip photonic sensors and nonlinear devices. Ideally, slot waveguide features a large evanescent field ratio and strong electric field intensity in the slot, leading to a high waveguide sensitivity. Unfortunately, the microring resonator (MRR) based on the slot waveguide suffers the less steep spectral slope due to the low quality factor induced by the huge optical propagation loss of the slot waveguide. In this work, a novel dual mode-splitting resonator based on the slot waveguide is proposed and demonstrated to steepen the slope of lineshapes. The device is implemented by two racetrack resonators based on a slot waveguide and a feedback waveguide to introduce coherent optical mode interference, which could induce mode-splitting resonance (MR) with sharp asymmetry line shape and large extinction ratio (ER). The proposed device is fabricated by the standard complementary metal-oxide-semiconductor (CMOS) technologies on silicon-on-insulator (SOI) platform, and the characterization results show dual MRs with an ER of 45.0 dB and a slope rate (SR) of 58.3 dB/nm, exhibiting a much steeper lineshape than that of the conventional MRR with slot waveguide. And the resonance can be tuned efficiently by applying various voltages of the TiN microheater. Investigations in dual MRs devices promote many potential applications in the field of optical switching, optical modulating, and on-chip optical sensing.

Robust therapeutic effects on COVID-19 of novel small molecules: Alleviation of SARS-CoV-2 S protein induction of ACE2/TMPRSS2, NOX2/ROS, and MCP-1.

While new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constantly emerge to prolong the pandemic of COVID-19, robust and safe therapeutics are in urgent need. During the previous and ongoing fight against the pandemic in China, Traditional Chinese Medicine (TCM) has proven to be markedly effective in treating COVID-19. Among active ingredients of TCM recipes, small molecules such as quercetin, glabridin, gallic acid, and chrysoeriol have been predicted to target viral receptor angiotensin-converting enzyme 2 (ACE2) via system pharmacology/molecular docking/visualization analyses. Of note, endothelial dysfunction induced by oxidative stress and inflammation represents a critical mediator of acute respiratory distress syndrome (ARDS) and multi-organ injuries in patients with COVID-19. Hence, in the present study, we examined whether quercetin, glabridin, gallic acide and chrysoeriol regulate viral receptors of ACE2 and transmembrane serine protease 2 (TMPRSS2), redox modulator NADPH oxidase isoform 2 (NOX2), and inflammatory protein of monocyte chemoattractant protein-1 (MCP-1) in endothelial cells to mediate therapeutic protection against COVID-19. Indeed, quercetin, glabridin, gallic acide and chrysoeriol completely attenuated SARS-CoV-2 spike protein (S protein)-induced upregulation in ACE2 protein expression in endothelial cells. In addition, these small molecules abolished S protein upregulation of cleaved/active form of TMPRSS2, while native TMPRSS2 was not significantly regulated. Moreover, these small molecules completely abrogated S protein-induced upregulation in NOX2 protein expression, which resulted in alleviated superoxide production, confirming their preventive efficacies against S protein-induced oxidative stress in endothelial cells. In addition, treatment with these small molecules abolished S protein induction of MCP-1 expression. Collectively, our findings for the first time demonstrate that these novel small molecules may be used as novel and robust therapeutic options for the treatment of patients with COVID-19, via effective attenuation of S protein induction of endothelial oxidative stress and inflammation.

Therapeutic Mechanism and Key Active Ingredients of Shenfu Injection in Sepsis: A Network Pharmacology and Molecular Docking Approach.

At present, although the early treatment of sepsis is advocated, the treatment effect of sepsis is unsatisfactory, and the mortality rate remains high. Shenfu injection (SFI) has been used to treat sepsis with good clinical efficacy. Based on network pharmacology, this study adopted a new research strategy to identify the potential therapeutic targets and key active ingredients of SFI for sepsis from the perspective of the pathophysiology of sepsis. This analysis identified 28 active ingredients of SFI based on UHPLC-QQQ MS, including 18 ginsenosides and 10 aconite alkaloids. 59 targets were associated with the glycocalyx and sepsis pathways. Based on the number of targets related to the pathophysiological process of sepsis, we identified songorine, ginsenoside Rf, ginsenoside Re, and karacoline as the key active ingredients of SFI for the treatment of sepsis. According to the cluster analysis of MCODE and the validation on the GEO dataset, LGALS3, BCHE, AKT1, and IL2 were identified as the core targets. This study further explored the therapeutic mechanism and the key active ingredients of SFI in sepsis and provided candidate compounds for drug development.

A systematic review of the efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia.

BACKGROUND: Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications. METHODS: Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings. RESULTS: Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention. CONCLUSIONS: Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.