Thai traditional medicines reduce CD147 levels in lung cells: Potential therapeutic candidates for cancers, inflammations, and COVID-19.

ETHNOPHARMACOLOGICAL RELEVANCE: The cluster of differentiation 147 (CD147) is identified as the signaling protein relevant importantly in various cancers, inflammations, and coronavirus disease 2019 (COVID-19) via interacting with extracellular cyclophilin A (CypA). The reduction of CD147 levels inhibits the progression of CD147-associated diseases. Thai traditional medicines (TTMs): Keaw-hom (KH), Um-ma-ruek-ka-wa-tee (UM), Chan-ta-lee-la (CT), and Ha-rak (HR) have been used as anti-pyretic and anti-respiratory syndromes caused from various conditions including cancers, inflammations, and infections. Thus, these medicines would play a crucial role in the reduction of CD147 levels. AIM OF THE STUDY: This article aimed to investigate the effects of KH, UM, CT, and HR for reducing the CD147 levels through in vitro study. Additionally, in silico study was employed to screen the active compounds reflexing the reduction of CD147 levels. MATERIALS AND METHODS: The immunofluorescent technique was used to evaluate the reduction of CD147 levels in human lung epithelial cells (BEAS-2B) stimulated with CypA for eight extracts of KH, UM, CT, and HR obtained from water decoction (D) and 70% ethanol maceration (M) including, KHD, UMD, CTD, HRD, KHM, UMM, CTM, and HRM. RESULTS: UM extracts showed the most efficiency for reduction of CD147 levels in the cytoplasm and perinuclear of BEAS-2B cells stimulated with CypA. Phenolic compounds composing polyphenols, polyphenol sugars, and flavonoids were identified as the major chemical components of UMD and UMM. Further, molecular docking calculations identified polyphenol sugars as CypA inhibitors. CONCLUSIONS: UMD and UMM are potential for reduction of CD147 levels which provide a useful information for further development of UM as potential therapeutic candidates for CD147-associated diseases such as cancers, inflammations, and COVID-19.

Effect of Nano-selenium on Biological Mechanism of Goblet Cells of the Small Intestine Within Laying Hen.

Dietary selenium intake within the normal physiological range is critical for various supporting biological functions. However, the effect of nano-selenium on biological mechanism of goblet cells associated with autophagy is largely unknown.The purpose of this study was to investigate the effect of nano-selenium on the mucosal immune-defense mechanism of goblet cells (GCs) in the small intestine of laying hens.The autophagy was determined by using specific markers. Nano-selenium-treated group of immunohistochemistry (IHC), immunofluorescence (IF), and western blotting (WB) results indicated the strong positive immune signaling of microtubule-associated light chain (LC3) within the mucosal surface of the small intestine. However, weak expression of LC3 was observed in the 3-methyladenine autophagy inhibitor (3-MA) group. IHC and IF staining results showed the opposite tendency for LC3 of sequestosome 1 (P62/SQSTM1). P62/SQSTM1 showed strong positive immune signaling within the mucosal surface of the small intestine of the 3-MAgroup, and weak immune signaling of P62/SQSTM1 in the nano-selenium-treated group. Moreover, pinpointing autophagy was involved in the mucosal production and enrichment of mucosal immunity of the GCs. The morphology and ultrastructure evidence showed that the mucus secretion of GCs was significantly increased after nano-selenium treatment confirmed by light and transmission electron microscopy. Besides that, immunostaining of IHC, IF and WB showed that autophagy enhanced the secretion of Mucin2 (Muc2) protein in nano-selenium-treated group. This work illustrates that the nano-selenium particle might enhance the mucosal immune-defense mechanism via the protective role of GCs for intestinal homeostasis through autophagy.

Saltiness enhancement by "má là" umami flavor in NaCl model aqueous and oil-added systems.

The health concerns associated with high dietary sodium and the quest for a sensory experience have prompted the need for new strategies that can reduce the salt content of foods and have good acceptability. To investigate the cross-modal interaction effects of "má là" umami flavor (total of eight carriers) on the saltiness perception and effective sodium reduction in low-to-strong NaCl aqueous solutions (0.203 %-1.39 %) and oil-added systems (5 %, 10 %, 15 %, 20 %, 25 % canola oil, wt%), sixteen assessors were selected and two methods including saltiness intensity comparison with a category scale and rating with a generalized Labeled Magnitude Scale (gLMS) were used. The results showed PnSnUn carriers significantly enhance saltiness at moderate-to-strong NaCl solutions, and higher saltiness intensity with the addition of canola oil, especially at 25 % oil level. In addition, based on the developed Stevens' power function the sodium reduction was calculated, it was evident that two "má là" umami flavor combinations (one flavor combination was low "má", low "là" and moderate umami, and the other flavor combination with moderate "má", low "là" and moderate umami) were found to perform best with maximum sodium reduction of 18.88 % and 18 %, respectively, and when incorporating 25 % canola oil, the maximum sodium reduction raised by approximately 10 % (to 28.00 % and 28.42 %). This research not only confirmed the positive modulating effect of the "má là" umami flavor on saltiness perception in NaCl solutions, but also showed that the presence of oil further enhanced this effect. This work offered a new and promising insight into the development of foods with reduced sodium content while maintaining the saltiness properties.

Relieving psychological stress and improving sleep quality by bergamot essential oil use before bedtime and upon awakening: A randomized crossover trial.

OBJECTIVES: The COVID-19 pandemic increased psychological stress and decreased sleep quality, especially among young people. Aromatherapy alleviates psychological stress, and bergamot essential oil helps improve depression. This study aimed to verify whether bergamot essential oil use alleviates psychological stress due to the COVID-19 pandemic and improves sleep quality and morning wakefulness. DESIGN: A placebo-controlled, randomized, open-label, two-arm, two-period crossover trial. INTERVENTIONS: Each intervention period was 1 week, with a 1-week washout period between the two periods. Participants used a bergamot or placebo spray before bedtime and upon awakening in each period. MAIN OUTCOME MEASURES: The primary outcome measures were sleep quality and morning wakefulness, assessed using the Ogri-Shirakawa-Azumi sleep inventory MA version (OSA-MA). The secondary outcome measures were depression, anxiety, and stress, assessed using the Depression Anxiety Stress Scales-21 (DASS-21). RESULTS: A total of 48 university students participated in the study. A significant improvement was observed in "sleepiness on rising," "refreshing on rising," and "sleep length" in the bergamot group. Additionally, a significant improvement was observed in depression, anxiety, and stress. CONCLUSION: Using bergamot essential oil before bedtime helps relax the mind and body and provides sound sleep. It also improves mood and wakefulness when used upon awakening. Using aromatic essential oils is expected to relieve psychological stress and improve sleep quality and morning wakefulness.

A Bioactive Compound-Loaded Zinc-Aminoclay Encapsulated, Pickering Emulsion System for Treating Acne-Inducing Microbes.

Acne is a common skin condition caused by the growth of certain bacteria. Many plant extracts have been investigated for their potential to combat acne-inducing microbes, and one such plant extract is microwave-assisted Opuntia humifusa extract (MA-OHE). The MA-OHE was loaded onto zinc-aminoclay (ZnAC) and encapsulated in a Pickering emulsion system (MA-OHE/ZnAC PE) to evaluate its therapeutic potential against acne-inducing microbes. Dynamic light scattering and scanning electron microscopy were used to characterize MA-OHE/ZnAC PE with a mean particle diameter of 353.97 nm and a PDI of 0.629. The antimicrobial effect of MA-OHE/ZnAC was evaluated against Staphylococcus aureus (S. aureus) and Cutibacterium acnes (C. acnes), which contribute to acne inflammation. The antibacterial activity of MA-OHE/ZnAC was 0.1 and 0.025 mg/mL to S. aureus and C. acnes, respectively, which were close to naturally derived antibiotics. Additionally, the cytotoxicity of MA-OHE, ZnAC, and MA-OHE/ZnAC was tested, and the results showed that they had no cytotoxic effects on cultured human keratinocytes in a range of 10-100 µg/mL. Thus, MA-OHE/ZnAC is suggested to be a promising antimicrobial agent for treating acne-inducing microbes, while MA-OHE/ZnAC PE is a potentially advantageous dermal delivery system.

Inhibiting virus replication and excessive inflammatory response: Mechanism of combined prescription of Ma-Xing-Shi-Gan decoction and Xiao-Chai-Hu decoction against influenza virus.

ETHNOPHARMACOLOGICAL RELEVANCE: The combined prescription of two classical decoctions (Ma-Xing-Shi-Gan decoction with Xiao-Chai-Hu decoction), named as San-Yang-He-Zhi (SYHZ) decoction, has been widely used for the treatment of influenza virus (IFV) infections for decades. AIM OF THE STUDY: This study aimed to evaluate the anti-influenza effect of SYHZ decoction and explore the underlying mechanism. MATERIALS AND METHODS: The ingredients of SYHZ decoction were analyzed by mass spectrometry. An animal model of IFV infection was established by challenging C57BL/6J mice with PR8 virus. Three groups of mice were infected with lethal or non-lethal doses of IFV, then followed by oral administration of phosphate-buffered saline (PBS), or SYHZ, or oseltamir; blank control mice (without IFV infection) were treated with PBS. Survival rate, Lung index, colon length, body weight loss and IFV viral load were measured 7 days post infection; histology and electron-microscopy examinations of lung tissue were performed; cytokine and chemokine levels in lung and serum were measured; and the intestinal metagenome, the cecum metabolome, and the lung transcriptome were analyzed. RESULTS: SYHZ treatment significantly improved survival rate compared with PBS (40% vs 0%); improved lung index, colon length, and body weight loss; and alleviated lung histological damage and viral load. SYHZ-treated mice had significantly lower levels of IL-1ß, TNF-α, IL-6, CCL2, CXCL10 in lung and serum, and increased levels of multiple bioactive components in cecum. Pro-inflammatory cytokines, Toll- and NOD-like receptors, pro-apoptosis molecules, and lung-injury-related proteins were downregulated in SYHZ mice, whereas surfactant protein and mucin were upregulated. The NOD-like receptor pathway, Toll-like receptor pathway, and NF-κB pathway were downregulated by SYHZ treatment. CONCLUSIONS: SYHZ decoction alleviated IFV infection in a mouse model. Multiple bioactive ingredients of SYHZ may inhibit replication of IFV and suppress excessive immune response.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice.

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Metabolomics integrated network pharmacology reveals the mechanism of Ma-Mu-Ran Antidiarrheal Capsules on acute enteritis mice.

Acute enteritis (AE) is a type of digestive disease caused by biochemical factors that irritate the intestinal tract or pathogenic bacteria that infect it. In China, Ma-Mu-Ran Antidiarrheal Capsules (MMRAC) have been applied against diarrhea caused by AE and bacillary dysentery for many years, but the underlying mechanisms of their beneficial effects are not known. In the present study, network pharmacology and metabolomics were performed to clarify the active ingredients of MMRAC and explore the specific mechanism of MMRAC on AE mice. A total of 43 active components of MMRAC with 87 anti-AE target genes were identified, and these target genes were enriched in IL-17 and HIF-1 signaling pathways. Integration analysis revealed that purine metabolism was the critical metabolic pathway by which MMRAC exerted its therapeutic effect against AE. Specifically, MAPK14, MMP9, PTGS2, HIF1A, EGLN1, NOS2 were the pivotal targets of MMRAC for the treatment of AE, and Western blot analysis revealed MMRAC to decrease protein levels of these pro-inflammatory signaling molecules. According to molecular docking, these key targets have a strong affinity with the MMRAC compounds. Collectively, MMRAC relieved the colon inflammation of AE mice via regulating inflammatory signaling pathways to reduce hypoxia and improved energy metabolism.

The "teacher" and martial arts: A psychobiographical analysis of Jack Ma as a business change agent.

OBJECTIVE: Scholars have conducted in-depth research on social change agents, but there are few collaborative studies in this realm between sociology and psychology. From the perspective of psychobiography, this before study uses Jung's Analytical Psychology as a theoretical framework to explore Jack Ma's influence on business change, thereby revealing the deep motivation behind Jack Ma's sudden retirement and choice to be a teacher. METHOD: This study has collected primary and secondary data about Jack Ma. QSR Nvivo 11.0 was used to encode the text based on video transcription, and then the data were analyzed. This study refers to the key factors of growth and follows the primary indicators of psychological saliency to sort out the data and find out what has special psychological significance, and then conducts three coding processes. RESULTS: This study found that the teacher complex and the martial arts complex are the breakthrough points to understand the business innovator Jack Ma. CONCLUSION: Jack Ma shapes the image of ordinary teachers through his image management strategy, conceals his deep internal martial arts complex, and balances the displayed martial arts personality mask. He has achieved great success in business innovator, while drawing on his internal personality conflicts to his advantage.

Effects of modified Maxing Shigan Decoction combined with acupoint application of Traditional Chinese Medicine on inflammatory indicators and pulmonary function in patients with acute exacerbation of chronic obstructive pulmonary disease with syndrome of phlegm-heat accumulated in the lung / 国际中医中药杂志

Objective:To observe the clinical effects of modified Maxing Shigan Decoction combined with acupoint application of Traditional Chinese Medicine (TCM) on inflammatory indicators and pulmonary function in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with syndrome of phlegm-heat accumulated in the lung.Methods:Prospective cohort study. Eighty AECOPD patients with syndrome of phlegm-heat accumulated in the lung, who met the inclusion criteria in our hospital from October 2020 to January 2022 were included, and randomized into two groups by random number table methods, 40 in each group. The control group received conventional therapy of Western medicine, while the treatment group received modified Maxing Shigan Decoction combined with acupoint application of TCM on the basic treatment of control group. Both groups were treated for a course of 14 days. The white blood count (WBC) and percentage of neutrophil (NE%) were detected by automatic blood cell analyzer. Levels of C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay (ELISA). Pulmonary function parameters including forced expiratory volume in one second (FEV1), percentage of forced expiratory volume in one second (FEV1%), forced vital capacity (FVC) and FEV1/FVC were detected by spirometry. Meantime, the adverse reactions and clinical responsive rate were recorded in both groups.Results:The overall responsive rate was 90.0% (36/40) in treatment group, which had statistically significant difference with 70.0% (28/40) in control group (χ 2=5.00, P=0.025). After treatment, plasma WBC [(4.15±1.02)×10 9/L vs. (7.53±1.27)×10 9/L, t=13.12], NE% [(0.50±0.12)% vs. (0.65±0.13)%, t=5.36] and serum CRP [(8.12±5.58)mg/L vs. (25.15±8.50)mg/L, t=10.59] in the treatment group were significantly lower than those in the control group ( P<0.05). The FEV1 [(1.94±0.23)L vs. (1.71±0.35)L, t=3.47], FEV1% [(88.25±9.21)% vs. (74.10±8.13)%, t=7.29], FVC [(3.85±0.31)L vs. (3.12±0.23)L, t=12.29] and FEV1/FVC [(86.12±7.18)% vs. (75.30±8.32)%, t=6.23] in the treatment group were significantly higher than those in the control group ( P<0.05). The adverse reaction rate during treatment period yielded no significant difference between two groups ( P>0.05). Conclusion:Application of modified Maxing Shigan Decoction combined with acupoint application of TCM in the treatment of AECOPD with syndrome of phlegm-heat accumulated in the lung can effectively attenuate inflammation response and ameliorate the pulmonary function.

Clinical study of Banxia Baizhu Tianma Decoction combined with modified Buyang Huanwu Decoction and routine western medicine in the treatment of ischemic stroke with qi-deficiency blood stasis syndrome / 国际中医中药杂志

Objective:To evaluate the effect of Banxia Baizhu Tianma Decoction combined with modified Buyang Huanwu Decoction and routine western medicine on ischemic stroke.Methods:Prospective cohort study. According to random number table method, 120 patients with ischemic stroke who met inclusion criteria in the hospital were divided into control group and treatment group, 60 in each group. The control group was given routine western medicine, while the treatment group was additionally given Banxia Baizhu Tianma Decoction and modified Buyang Huanwu Decoction. All were treated for 4 weeks. The severity of neurological deficits was evaluated by National Institute of Health Stroke Scale (NIHSS). The activities of daily living were evaluated by Barthel index. The high blood shear viscosity (HWBV), low blood shear viscosity (LWBV), plasma fibrinogen (FIB) and plasma viscosity (PV) were detected by full-automatic blood rheometer. The levels of MDA, SOD and NO were detected by ELISA. The clinical responsive rate was assessed.Results:The differences in total response rate between treatment group and control group were statistically significant [93.3% (56/60) vs. 75.0% (45/60), χ2=7.56, P=0.006]. After treatment, NIHSS score in treatment group was significantly lower than that in control group ( t=2.38, P=0.019), while Barthel index was significantly higher than that in control group ( t=13.28, P<0.01). After treatment, HWBV [(5.02±0.13) mPa?s vs. (6.18±0.28) mPa?s, t=29.11], LWBV [(1.18±0.21) mPa?s vs. (1.73±0.32) mPa?s, t=11.13], FIB [(2.26±0.28) g/L vs. (3.13±0.39) g/L, t=14.04] and PV [(8.87±1.44) mPa?s vs. (10.34±1.31) mPa?s, t=5.85] in treatment group were significantly lower than those in control group ( P<0.01), and the MDA [(4.14±1.23) mmol/L vs. (5.23±1.35) mmol/L, t=204.30] in treatment group was significantly lower than that in control group ( P<0.01), and levels of SOD [(113.34±0.28) mg/L vs. (96.59±0.57) mg/L, t=4.62] and NO [(26.01±3.26) μmol/L vs. (20.84±3.74) μmol/L, t=8.07] in treatment group were significantly higher than those in control group ( P<0.01). Conclusion:The Banxia Baizhu Tianma Decoction combined with modified Buyang Huanwu Decoction and routine western medicine can repair nerve function, improve hemorheology, oxidative stress indexes, clinical curative effect and activities of daily living in patients with ischemic stroke.

Clinical observation of Mahuang Fuzi Xixin Decoction combined with balanced acupuncture in the treatment of Migraine with Yang deficiency and cold coagulation / 国际中医中药杂志

Objective:To observe the clinical efficacy of Mahuang Fuzi Xixin Decoction combined with balanced acupuncture in the treatment of migraine with yang deficiency and cold congealing syndrome.Methods:Randomized controlled trial. Totally 91 cases of migraine with yang deficiency and cold congealing syndrome in our hospital from March 2021 to May 2022 were selected and divided into 45 cases in the Western medicine group and 46 cases in the integrated Chinese and Western medicine group according to random number table method. The Western medicine group took flunarizine hydrochloride capsules orally, and the integrated Chinese and Western medicine group combined ephedrine and aconiti asarum decoction + balanced acupuncture treatment on the basis of the Western medicine group. Both groups were treated for 1 month. Traditional Chinese Medicine syndrome score was performed before and after treatment, the degree of headache was assessed by VAS scale, and the impact of headache on life was assessed by Headache Impact Test-6 (HIT-6); the levels of 5-hydroxytryptamine (5-HT) and calcitonin gene related peptide (CGRP) were determined by radioimmunoassay. The adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 82.22% (37/45) in the Western medicine group and 95.65% (44/46) in the integrated Chinese and Western medicine group, with statistical significance ( χ2=4.20, P=0.041). After treatment, the scores of headache, hair, urine and cold limbs in the integrated Chinese and Western medicine group were lower than those in the Western medicine group ( t values were 18.49, 22.29, 21.31, 27.49, P<0.01), and the scores of VAS and HIT-6 were lower than those in the Western medicine group ( t values were 23.20, 9.33, P<0.01). After treatment, the level of 5-HT in the integrated Chinese and Western medicine group [(98.34±6.23) μg/L vs. (85.23±4.21) μg/L, t=11.74] was higher than that of the Western medicine group ( P<0.01); CGRP [(11.24±1.99) ng/L vs. (15.22±2.52) ng/L, t=8.37] was lower than that of the Western medicine group ( P<0.01). During treatment, the incidence of adverse reactions was 2.22% (1/45) in the Western medicine group and 2.17% (1/46) in the integrated Chinese and Western medicine group, without statistical significance ( P>0.05). Conclusion:Mahuang Fuzi Xixin Decoction combined with balanced acupuncture can effectively improve the clinical symptoms and life quality of patients of migraine with yang deficiency and cold congealing, and the clinical efficacy can be promoted.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology.

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf in the Gramineae family. Coix seed has a sweet, light taste, and a cool nature. Coix seed enters the spleen, stomach, and lung meridians. It has the effects of promoting diuresis and dampness, strengthening the spleen to prevent diarrhea, removing arthralgia, expelling pus, and detoxifying and dispersing nodules. It is used for the treatment of edema, athlete's foot, poor urination, spleen deficiency and diarrhea, dampness and obstruction, lung carbuncle, intestinal carbuncle, verruca, and cancer. The medicinal and health value is high, and it has been included in the list of medicinal and food sources in China, which has a large development and application space. This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times, aiming to provide reference for further research on Coix seed and contribute to its clinical application and development. Through the analysis of the traditional Chinese patent medicines, and simple preparations and related health food of Coix seed queried by Yaozhi.com, the source, function, and dosage form of Coix seed were comprehensively analyzed, with a view of providing a reference for the development of Coix seed medicine and food.

Pharmaceutical and pharmacological studies of Shen Ma Yi Zhi granule for prevention of vascular dementia: A review.

Background: With dementia significantly increasing hospitalization and disability rates, worldwide aging of the population presents major challenges to public health. The majority of cases of cognitive dysfunction among the elderly, however, are characterized by an identifiable, preventable and treatable vascular component. As such, increased study of preventative methods in the context of dementia is warranted. Traditional Chinese medicine compounds have been reported to be neuroprotective and improve cognitive function via a variety of mechanisms. Shen Ma Yi Zhi granule (SMYZG) is one such collection of compounds that has been proven clinically effective. Pharmacological mechanisms of action, pharmacokinetics and clinical applications of SMYZG have been previously studied using a variety of vascular dementia animal models. SMYZG activates and regulates four main signaling pathways relevant to vascular dementia including the AMPK/PPARα/PGC-1α/UCP2, Nrf2/HO-1, HIF-1/VEGF/Notch, and VEGF/Flk-1/p8 MAPK pathways. Furthermore, SMYZG influences anti-inflammatory and anti-oxidant stress responses, reverses demyelination of brain white matter and vascular endothelium, regulates pericyte function and normalizes mitochondrial metabolism. Neuroprotective effects of SMYZG, as well as those promoting regeneration of vascular endothelium, have also been reported in studies of rat models of vascular dementia. Future research concerning SMYG is warranted for development of vascular dementia preventative management strategies.

Natural carbazole alkaloid murrayafoline A displays potent anti-neuroinflammatory effect by directly targeting transcription factor Sp1 in LPS-induced microglial cells.

Neuroinflammation is a leading cause for neurological disorders. Carbazole alkaloids, isolated from the medicinal plants of Murraya species (Rutaceae), have exhibited wide pharmacological activities particularly for neuroinflammation. However, its underlying cellular targets and molecular mechanisms still remain unclear. In current study, we found that murrayafoline A (MA), a carbazole alkaloid obtained from Murraya tetramera, potently inhibited the production of neuroinflammation mediators, such as nitric oxide (NO), TNF-α, IL-6 and IL-1ß in LPS-induced BV-2 microglial cells. Then, we performed thermal proteome profiling (TPP) strategy to identify Specificity protein 1 (Sp1) as a potential cellular target of MA. Moreover, we performed surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DRATS) assays to confirm the direct interaction between MA and Sp1. Furthermore, we downregulated Sp1 expression in BV2 cells using siRNA transfection, and observed that Sp1 knockdown significantly antagonized MA-mediated inhibition of neuroinflammation mediator production. Meanwhile, Sp1 knockdown also markedly reversed MA-mediated inactivation of IKKß/NF-κB and p38/JNK MAPKs pathways. Finally, in vivo studies revealed that MA significantly suppressed the expression of Iba-1, TNF-α, and IL-6, while increased the number of Nissl bodies in the brains of LPS-induced mice. Taken together, our study demonstrated that MA exerted obvious anti-neuroinflammation effect by directly targeting Sp1, thereby inhibiting NF-κB and MAPK signaling pathways. Our findings also provided a promising direction of pharmacological targeting Sp1 for anti-neuroinflammation therapeutics as well as novel agent development.

Two Laminaria japonica polysaccharides with distinct structure characterization affect gut microbiota and metabolites in hyperlipidemic mice differently.

Our previous study found dietary mannogluconic acid (MA) and fucogalactan sulfate (FS) from Laminaria japonica have distinct structure characterization and potential hypolipidemic effects in vitro. Herein, we compared the benefits of MA and FS on hyperlipidemia. The result showed only FS treatment decreased body weight and serum cholesterol levels. Compared with MA, FS was more effective in mitigating hepatic fat accumulation, promoting GSH-Px activity, reducing the MDA formation, and lowering the level of TNF-α in liver. Gut microbiota and metabolism analysis revealed that FS increased the relative abundance of beneficial bacteria and boosted the level of short chain fatty acids. Particularly, taurine and 3α,7α,12α-trihydroxy-24-oxo-5-ß-cholestanoyl CoA were upregulated by FS, which might attribute to the increased Oscillibacter and thus affect the enterohepatic circulation of bile acids and serum TC level. Therefore, FS with more branches and sulfate ester groups could be a good lipid-lowering dietary supplement.

Improved classification performance of EEG-fNIRS multimodal brain-computer interface based on multi-domain features and multi-level progressive learning.

Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) have potentially complementary characteristics that reflect the electrical and hemodynamic characteristics of neural responses, so EEG-fNIRS-based hybrid brain-computer interface (BCI) is the research hotspots in recent years. However, current studies lack a comprehensive systematic approach to properly fuse EEG and fNIRS data and exploit their complementary potential, which is critical for improving BCI performance. To address this issue, this study proposes a novel multimodal fusion framework based on multi-level progressive learning with multi-domain features. The framework consists of a multi-domain feature extraction process for EEG and fNIRS, a feature selection process based on atomic search optimization, and a multi-domain feature fusion process based on multi-level progressive machine learning. The proposed method was validated on EEG-fNIRS-based motor imagery (MI) and mental arithmetic (MA) tasks involving 29 subjects, and the experimental results show that multi-domain features provide better classification performance than single-domain features, and multi-modality provides better classification performance than single-modality. Furthermore, the experimental results and comparison with other methods demonstrated the effectiveness and superiority of the proposed method in EEG and fNIRS information fusion, it can achieve an average classification accuracy of 96.74% in the MI task and 98.42% in the MA task. Our proposed method may provide a general framework for future fusion processing of multimodal brain signals based on EEG-fNIRS.

Ma's bamboo-based medicinal moxibustion therapy of low back pain in lumbar disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: Lumbar disc herniation (LDH) is a common and frequently occurring disease in clinics. Low back pain and sciatica are the presenting symptoms of LDH. To some extent, it can be considered that measures with the capability to improve low back pain or sciatica have the potential to treat LDH. Ma's bamboo-based medicinal moxibustion therapy can effectively reduce the degree of low back pain and has been widely used. Studies of small sample size have seen significant improvement on pain relief. The aim of this trial is to evaluate the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy in the treatment of LDH low back pain. METHODS/DESIGN: The trial is a multicenter, randomized, parallel-group, non-inferiority study. Three hundred and twelve patients will be randomly assigned to a Ma's bamboo-based medicinal moxibustion group (n=156) and an acupuncture group (n=156). Patients in each group will receive treatment every day, 6 times a week, 12 times in total. Follow-up will be conducted 14 days after treatment. The primary outcome will be the visual analog scale(VAS) at baseline, after 6 times of treatment, end of treatment, and follow-up. The secondary outcomes will include Oswestry disability indexes (ODI), modified Japanese Orthopaedic Association low back pain (M-JOA) score, serum ß-endorphin (ß-EP), and serum substance P (SP). ß-EP and SP, as well as safety evaluation indexes (routine blood, liver, and kidney function and electrocardiogram), will be measure at baseline and after the end of treatment. The number, nature, and severity of adverse events will be recorded. DISCUSSION: The results of the trial will compare the efficacy of low back pain in LDH between Ma's bamboo-based medicinal moxibustion group and the acupuncture group and will be expected to make a systematic and objective evaluation of the clinical efficacy and safety of Ma's bamboo-based medicinal moxibustion therapy. TRIAL REGISTRATION: ChiCTR2000038725 . Registered on 29 September 2020.

Irradiation of localized prostate cancer in the elderly: A systematic literature review.

Purpose: To analyze the literature that addresses radiation therapy for intermediate and high-risk prostate cancer (PC) in the elderly. Patients and methods: A PubMed literature search was conducted including articles from 01/01/2000 to 30/06/21, with the following keywords: PC, radiotherapy/brachytherapy and elderly. The analysis mainly focused on the issue of under-treatment in the elderly and the benefit/risk balance of irradiation. Results: Of the 176 references analyzed, 24 matched the selection criteria. The definition of "elderly patient" varied from 70 to 80 years. The analysis was impacted by the inhomogeneous primary end points used in each cohort. Age was often an obstacle to radical treatment, with a subsequent risk of under-treatment, particularly in patients with a poorer prognosis. However, comparable elderly oncological outcomes were compared to younger patients, both with external beam radiotherapy alone or combined with brachytherapy boost. Late toxicity rates are low and most often comparable to younger populations. However, a urinary over- toxicity was observed in the super-elderly (>80 years) after brachytherapy boost. The use of ADT should be considered in light of comorbidities, and may even be deleterious in some patients. Conclusion: Due to the increase in life expectancy, the management of PC in the elderly is a challenge for patients, clinicians and health insurance payers. Except for unfit men, elderly patients remain candidates for optimal curative treatment (i.e. regardless of age) after oncogeriatric assessment. More solid data from prospective trials conducted specially in this population will provide better guidance in our daily clinical practice.

Therapeutic effect of Prosopis strombulifera (LAM) BENTH aqueous extract on a murine model of cutaneous leishmaniasis.

Background and aim: Prosopis strombulifera (Lam.) Benth is a rhizomatous shrub native from different zones of Argentine Republic. P. strombulifera aqueous extract (PsAE) has different effects and several biological activities have been reported. The goal of this study was to analyze the activity of PsAE on a murine model of cutaneous leishmaniasis caused by Leishmania amazonensis. Experimental procedure: PsAE was orally administered at 150 mg/animal/day on BALB/c mice infected in the right footpad (RFP) with 1 × 105 promastigotes of L. amazonensis. As a chemotherapeutic control of treatment, animals receive a commercial form of meglumine antimoniate (MA) (Glucantime®, Aventis, Paris, France). Results and conclusion: We observe that the size of RFP lesions of infected mice without treatment showed a grade of inflammation, ulceration and necrosis at the site of infection much greater than that observed with PsAE or MA treatment. Moreover, PsAE was capable of decreasing parasite burden and splenic index. Furthermore, PsAE treated mice showed a significant decrease in O.D. of total anti-Leishmania IgG antibody responses against L. amazonensis. This decrease was similar to those observed when the reference drug, MA, was used. This would indicate that PsAE treatment inhibits or delays disease progression in mice. In conclusion, our findings suggest that PsAE could be a potential candidate to be used, as a new therapeutic strategy, to treat cutaneous leishmaniasis caused by L. amazonensis.