Double-blinded, randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia.

Background: Accumulating evidence suggests that metabolic disorders, including type 2 diabetes mellitus (T2DM), can be treated with traditional Chinese medicine formulas, such as the Gegen Qinlian decoction (GQD). This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD. Methods: We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM. During the 12-week intervention, anthropometric measurements and diabetic traits were recorded every 4 weeks. Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing, liquid chromatography-mass spectrometry, and Bio-Plex panels. Results: Anti-diabetic effects were observed in the GQD group in the human trial. Specifically, glycated hemoglobin, fasting plasma glucose, and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group. Additionally, Faecalibacterium was significantly enriched in the GQD group, and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group. Moreover, Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin, fasting plasma glucose, and pro-inflammatory cytokines. Finally, the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzii (DSMZ 17677) in T2DM mouse model. Conclusions: GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota, alleviating metabolic disorders and the inflammatory state. Trial registration: Registry No. ChiCTR-IOR-15006626.

Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

In Every Detail: Spiritual Care in Pediatric Palliative Care Perceived by Healthcare Providers.

CONTEXT: Spiritual care is an essential domain of pediatric palliative care. The current mainland China faces a lack of national guidance and a shortage of specialized personnel to provide spiritual care in a traditional developing country. OBJECTIVES: To identify spiritual care in pediatric palliative care services in mainland China from the perspective of healthcare professionals. METHODS: A qualitative descriptive interview study was conducted individually with 27 participants: 14 physicians, seven nurses, and six social workers. The data were analyzed using thematic analysis. RESULTS: Participants described that the essence of spiritual support was provided "in every detail" throughout pediatric palliative care. Four major themes and eleven subthemes were identified. 1) Assessing spiritual needs: paying attention to different perspectives; considering religion, tradition, and culture; discovering spiritual needs behind other needs. 2) Facilitating spiritual exploration: being with the family; providing resources; guiding by providers' own faith; 3) Supporting connections: encouraging the building of personal bonds; facilitating the establishment of spiritual connections. 4) Relieving spiritual suffering: facilitating a family review of child's life; supporting building meaning in daily life; assisting in leaving a legacy for the child. CONCLUSION: This study illustrated that current spiritual support, though not formally organized, is provided individually in pediatric palliative care services in mainland China. Strategies for a practice guide, education and training for professionals, and cultural building need to be rationally developed to strengthen and structure spiritual support integrated into pediatric palliative care.

Extraction, purification, characteristics, bioactivities, prospects, and toxicity of Lilium spp. polysaccharides.

The genus Lilium has been widely used worldwide as a food and medicinal ingredient in East Asia for over 2000 years due to its higher nutritional and medicinal value. Polysaccharide is the most important bioactive ingredient in Lilium spp. and has various health benefits. Recently, Lilium spp. polysaccharides (LSPs) have attracted significant attention from industries and researchers due to their various biological properties, such as antioxidant, immunomodulatory, antitumor, antibacterial, hypoglycaemic, and anti-radiation. However, the development and utilization of LSP-based functional biomaterials and medicines are limited by a lack of comprehensive understanding regarding the structure-activity relationships (SARs), industrial applications, and safety of LSPs. This review provides an inclusive overview of the extraction, purification, structural features, bioactivities, and mechanisms of LSPs. SARs, applications, toxicities, and influences of structural modifications on bioactivities are also highlighted, and the potential development and future study direction are scrutinized. This article aims to offer a complete understanding of LSPs and provide a foundation for further research and application of LSPs as therapeutic agents and multifunctional biomaterials.

The Hydrolysis of Pigment-Protein Phycoerythrin by Bromelain Enhances the Color Stability.

Phycoerythrin (PE) is a natural protein-pigment complex with a strong pink color, but it is sensitive to thermal and light variations. In this study, PE was extracted from Porphyra haitanensis in a yield of 0.2% (w/w). The phycoerythrin hydrolysates (PEH) (3-10 kDa) were prepared by enzymatic hydrolysis of PE with bromelain (8000 U/g) at 47 °C for 30 min, with a degree of hydrolysis (DH) of 11.57 ± 0.39% and a color degradation rate of 7.98 ± 0.39%. The physicochemical properties of PEH were evaluated. The UV and fluorescence spectra indicated that bromelain changed the microenvironment around phycoerythrobilin (PEB). The infrared spectrum revealed that the bromelain hydrolysis increased the α-helix content of PEH. The scanning electron microscope showed that bromelain destroyed the dense and smooth structure of PE, resulting in irregular porous structures. The radical scavenging activities of DPPH and ABTS of PEH were increased relative to that of PE (p < 0.05). The thermal (50-80 °C)-, UV (0.5-3 h)-, visible light irradiation (2-8 h)-, and metal ion exposing stabilities of PEH were significantly improved (p < 0.05). This study provides a potential scheme for overcoming the sensitivity of PE to thermal and light variations and facilitates PEH as a natural colorant ingredient in food and pigment applications.

Randomized Trial on the Effect of Oral Potassium Chloride Supplementation on the Thiazide-Sensitive Sodium Chloride Cotransporter in Healthy Adults.

Introduction: The putative "renal-K switch" mechanism links dietary potassium intake with sodium retention and involves activation of the sodium chloride (NaCl) cotransporter (NCC) in the distal convoluted tubule in response to low potassium intake, and suppression in response to high potassium intake. This study examined NCC abundance and phosphorylation (phosphorylated NCC [pNCC]) in urinary extracellular vesicles (uEVs) isolated from healthy adults on a high sodium diet to determine tubular responses to alteration in potassium chloride (KCl) intake. Methods: Healthy adults maintained on a high sodium (∼4.5 g [200 mmol]/d) low potassium (∼2.3 g [60 mmol]/d) diet underwent a 5-day run-in period followed by a crossover study, with 5-day supplementary KCl (active phase, Span-K 3 tablets (potassium 24 mmol) thrice daily) or 5-day placebo administrated in random order and separated by 2-day washout. Ambulatory blood pressure (BP) and biochemistries were assessed, and uEVs were analyzed by western blotting. Results: Among the 18 participants who met analysis criteria, supplementary KCl administration (vs. placebo) was associated with markedly higher levels of plasma potassium and 24-hour urine excretion of potassium, chloride, and aldosterone. KCl supplementation was associated with lower uEV levels of NCC (median fold change (KCl/Placebo) = 0.74 [0.30-1.69], P < 0.01) and pNCC (fold change (KCl/Placebo) = 0.81 [0.19-1.75], P < 0.05). Plasma potassium inversely correlated with uEV NCC (R2 = 0.11, P = 0.05). Conclusions: The lower NCC and pNCC in uEVs in response to oral KCl supplementation provide evidence to support the hypothesis of a functional "renal-K switch" in healthy human subjects.

Rapid simultaneous removal of nitrogen and phosphorous by a novel isolated Pseudomonas mendocina SCZ-2.

Nitrogen (N) and phosphorous (P) removal by a single bacterium could improve the biological reaction efficiency and reduce the operating cost and complexity in wastewater treatment plants (WWTPs). Here, an isolated strain was identified as Pseudomonas mendocina SCZ-2 and showed high performance of heterotrophic nitrification (HN) and aerobic denitrification (AD) without intermediate accumulation. During the AD process, the nitrate removal efficiency and rate reached a maximum of 100% and 47.70 mg/L/h, respectively, under optimal conditions of sodium citrate as carbon source, a carbon-to-nitrogen ratio of 10, a temperature of 35 °C, and shaking a speed of 200 rpm. Most importantly, the strain SCZ-2 could rapidly and simultaneously eliminate N and P with maximum NH4+-N, NO3--N, NO2--N, and PO43--P removal rates of 14.38, 17.77, 20.13 mg N/L/h, and 2.93 mg P/L/h, respectively. Both the N and P degradation curves matched well with the modified Gompertz model. Moreover, the amplification results of functional genes, whole genome sequencing, and enzyme activity tests provided theoretical support for simultaneous N and P removal pathways. This study deepens our understanding of the role of HN-AD bacteria and provides more options for simultaneous N and P removal from actual sewage.

Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response.

Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation.

Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ supplementation on BP in mice, whether differences depend on the accompanying anion or the sodium (Na+) intake and molecular alterations in the kidney that may underlie BP changes. Relative to the control diet, BP was higher in mice fed a high NaCl (1.57% Na+) diet for 7 weeks or fed a K+-free diet for 2 weeks. BP was highest on a K+-free/high NaCl diet. Commensurate with increased abundance and phosphorylation of the thiazide sensitive sodium-chloride-cotransporter (NCC) on the K+-free/high NaCl diet, BP returned to normal with thiazides. Three weeks of a high K+ diet (5% K+) increased BP (predominantly during the night) independently of dietary Na+ or anion intake. Conversely, 4 days of KCl feeding reduced BP. Both feeding periods resulted in lower NCC levels but in increased levels of cleaved (active) α and γ subunits of the epithelial Na+ channel ENaC. The elevated BP after chronic K+ feeding was reduced by amiloride but not thiazide. Our results suggest that dietary K+ has an optimal threshold where it may be most effective for cardiovascular health.

Dihydrophenanthrenes and phenanthrenes from Dendrobium terminale.

Two previously undescribed dihydrophenanthrene derivatives (1 and 2) were isolated along with twelve known analogues from the whole plant of Dendrobium terminale. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis. The NMR data of known phenanthrene derivatives (7 and 9) were revised by 2D NMR. The isolated compounds were evaluated for cytotoxicity against three kinds of tumor cell lines (sw1990, HCT-116, and HepG2). Especially compounds 11 and 14 showed stronger antitumor effects, and the structure-activity relationship of these compounds was discussed.

Development and validation of an LC-MS/MS method for detection of glycyrol in rat plasma and its application to a pharmacokinetic study.

Licorice (Glycyrrhiza uralensis) is one of the most popular edible and medicinal plants and is widely used in Asia. Glycyrol (GC) is a major coumarin present in licorice that exhibits various biological activities. We aimed to develop a highly sensitive and rapid liquid chromatography coupled with mass spectrometry method for the quantitative determination analysis of GC in rat plasma. GC showed linear calibration ranges of 1-100 and 50-2,000 ng/ml with correlation coefficients >0.99. The average extraction recovery ranged from 113.26 to 114.84%, and the relative standard deviation of internal standard normalized matrix factors ranged from 6.36 to 9.46%. The intra-day and inter-day precisions of GC were <15%, and the accuracy ranged from 95.31 to 112.72%. Pharmacokinetic studies showed that GC was distributed in the body with a volume of distribution of 9.06 L/kg, and the initial plasma concentration was 3275.11 ng/ml. The area under the plasma concentration vs. time curve was 479.25 ng h/ml. It was rapidly eliminated with a terminal elimination half-life of 1.47 h and a clearance rate of 4.24 L/h/kg. The pharmacokinetic results can help us to better understand the pharmacological effects of GC in the body.

A Comprehensive Investigation on Potential Risk Factors for NSCL/P in a Rural District of Hebei Province, China.

Non syndromic cleft lip with or without palate (NSCL/P), one of the most common birth defects, is closely related to various risk factors. However, information regarding risk factors for NSCL/P in rural districts in China is very limited thus far. The objective of this study was designed to identify the potential risk factors for NSCL/P in rural districts.A comprehensive retrospective investigation including 435 NSCL/P patients and 402 healthy children was carried out in Hebei Province, China. Multiple logistic regression analysis and transmission disequilibrium test (TDT) were respectively used to identify non-genetic and genetic risk factors for NSCL/P, and then PLINK was used to explore the relationship between non-genetic and genetic risk factors.The results showed that maternal periconceptional exposure to pesticides and herbicides, as well as low parental education level were involved in the increased risk of NSCL/P, whereas maternal folic acid and multivitamin supplementation use during preconception period were associated with the reduced risk of NSCL/P. TDT analysis identified 2 single nucleotide polymorphisms (SNPs) (rs7078160 and rs4752028) in VAX1 and one SNP (rs17563) in BMP4 as the genetic risk factors for NSCL/P. Further analysis showed that the genetic risk factors were closely related with the negative non-genetic risk factors.Our study identified the potential risk factors for NSCL/P in rural districts, thus providing a theoretical basis for the prevention of NSCL/P occurrence.

Immune-related effects of compound astragalus polysaccharide and sulfated epimedium polysaccharide on newborn piglets.

This study aimed to evaluate the immune effects of compound astragalus polysaccharide and sulfated epimedium polysaccharide (APS-sEPS) on the peripheral blood lymphocyte and intestinal mucosa in newborn piglets. A total of 40 newborn piglets were randomly divided into four groups during a 25-day experiment, including APS-sEPS, APS, sEPS and control group. The results showed that supplementation with APS-sEPS to newborn piglets remarkably increased the physiological parameters, especially the WBC. In peripheral blood, piglets that received APS-sEPS showed the highest proliferation of T lymphocytes, the percentage of CD3 + CD4+ and CD3 + CD8+ cells were the highest on days 15 and 25 (p < 0.05). The serum concentrations of IFN-γ on days 7 and 15, and IL-4, IL-10, sIgA on days 7, 15 and 25 in APS-sEPS group were significantly higher than those in the control group (p < 0.05). Furthermore, the villus length and the ratio of villus length to crypt depth in APS-sEPS group were both significantly increased compared to that of control group (p < 0.05). In the duodenum, jejunum and illume, the concentrations of IFN-γ, IL-10, total IgG and sIgA in APS-sEPS group were all significantly higher than that in control group (p < 0.05). In intestinal mucosa, APS-sEPS significantly increased the expression of NF-κB and IRF-3 mRNA in each section of small intestine of piglets. Nevertheless, in the illume segment, the effect of APS-sEPS was more significant than that of APS and sEPS (p < 0.05). The expression of TLR4 was more significant than that of control group in duodenum only. The results from the present research provide evidence that the suckling piglets administered with APS-sEPS supplement exhibited enhanced immune function of peripheral blood lymphocyte and expression of specific antibodies, and ameliorated intestinal morphological development and increased activities of humoral immune response in the small intestine, which would be related to the activation of the TLR4-NF-κB signaling pathway and IRF3.

FtNAC31, a Tartary buckwheat NAC transcription factor, enhances salt and drought tolerance in transgenic Arabidopsis.

Tartary buckwheat [Fagopyrum tataricum (L.) Gaertn.] is a pseudocereal with strongly abiotic resistance. NACs, one of the largest plant-specific transcription factors (TFs), are involved in various stress responses. However, the characteristics and regulatory mechanisms of NAC TFs remain unclarified clearly in Tartary buckwheat (TB). In this study, it validated that salt, drought, and abscisic acid (ABA) stress significantly up-regulated the expression of NAC TF gene FtNAC31. Its coding protein has a C-terminal transactivated domain and localized in the nucleus, suggesting that FtNAC31 might play a transcriptional activation role in TB. Notably, overexpression of FtNAC31 lowered the seed germination rate upon ABA treatment and enhanced the tolerance to salt and drought stress in transgenetic Arabidopsis. Furthermore, under various stresses, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in FtNAC31 overexpressed lines exhibited a sharp increase trend. Meanwhile, the expression levels of several stress-associated genes including RD29A, RD29B, RD22, DREB2B, NCED3, and POD1, were dramatically upregulated in lines overexpressing FtNAC31. Altogether, overproduction of FtNAC31 could enhance the resistance to salt and drought stresses in transgenic Arabidopsis, which most likely functioned in an ABA-dependent way.

The Use of Deep Learning-Based Gesture Interactive Robot in the Treatment of Autistic Children Under Music Perception Education.

The purpose of this study was to apply deep learning to music perception education. Music perception therapy for autistic children using gesture interactive robots based on the concept of educational psychology and deep learning technology is proposed. First, the experimental problems are defined and explained based on the relevant theories of pedagogy. Next, gesture interactive robots and music perception education classrooms are studied based on recurrent neural networks (RNNs). Then, autistic children are treated by music perception, and an electroencephalogram (EEG) is used to collect the music perception effect and disease diagnosis results of children. Due to significant advantages of signal feature extraction and classification, RNN is used to analyze the EEG of autistic children receiving different music perception treatments to improve classification accuracy. The experimental results are as follows. The analysis of EEG signals proves that different people have different perceptions of music, but this difference fluctuates in a certain range. The classification accuracy of the designed model is about 72-94%, and the average classification accuracy is about 85%. The average accuracy of the model for EEG classification of autistic children is 85%, and that of healthy children is 84%. The test results with similar models also prove the excellent performance of the design model. This exploration provides a reference for applying the artificial intelligence (AI) technology in music perception education to diagnose and treat autistic children.

Herb-Drug Interaction Between Xiyanping Injection and Lopinavir/Ritonavir, Two Agents Used in COVID-19 Pharmacotherapy.

The global epidemic outbreak of the coronavirus disease 2019 (COVID-19), which exhibits high infectivity, resulted in thousands of deaths due to the lack of specific drugs. Certain traditional Chinese medicines (TCMs), such as Xiyanping injection (XYPI), have exhibited remarkable benefits against COVID-19. Although TCM combined with Western medicine is considered an effective approach for the treatment of COVID-19, the combination may result in potential herb-drug interactions in the clinical setting. The present study aims to verify the effect of XYPI on the oral pharmacokinetics of lopinavir (LPV)/ritonavir (RTV) using an in vivo rat model and in vitro incubation model of human liver microsomes. After being pretreated with an intravenous dose of XYPI (52.5 mg/kg) for one day and for seven consecutive days, the rats received an oral dose of LPV/RTV (42:10.5 mg/kg). Except for the t1/2 of LPV is significantly prolonged from 4.66 to 7.18 h (p < 0.05) after seven consecutive days pretreatment, the pretreatment resulted in only a slight change in the other pharmacokinetic parameters of LPV. However, the pharmacokinetic parameters of RTV were significantly changed after pretreatment with XYPI, particularly in treatment for seven consecutive days, the AUC0-∞ of RTV was significantly shifted from 0.69 to 2.72 h µg/mL (p < 0.05) and the CL exhibited a tendency to decrease from 2.71 L/h to 0.94 L/h (p < 0.05), and the t1/2 of RTV prolonged from 3.70 to 5.51 h (p < 0.05), in comparison with the corresponding parameters in untreated rats. After administration of XYPI, the expression of Cyp3a1 protein was no significant changed in rats. The in vitro incubation study showed XYPI noncompetitively inhibited human CYP3A4 with an apparent Ki value of 0.54 mg/ml in a time-dependent manner. Our study demonstrated that XYPI affects the pharmacokinetics of LPV/RTV by inhibiting CYP3A4 activity. On the basis of this data, patients and clinicians can take precautions to avoid potential drug-interaction risks in COVID-19 treatment.

Efficacy and safety of electroacupuncture treatment in the prevention of negative moods in healthy young men after 30 h of total sleep deprivation: study protocol for a single-center, single-blind, parallel-arm, randomized clinical trial.

BACKGROUND: Sleep deprivation (SD) among young adults is a major public health concern. In humans, it has adverse effects on mood and results in serious health problems. Faced with SD, persons may take precautionary measures to try and reduce their risk. The aim of this study is to evaluate the efficacy and safety of electroacupuncture (EA) for the prevention of negative moods after SD. In addition, we will do a comparison of the effects of EA on mood after SD at different time points. METHODS: This randomized controlled trial (RCT) will be performed at the First Affiliated Hospital of Changchun University of Chinese Medicine in China. The Standards for Reporting Interventions in Clinical Trials of Acupuncture 2010 will be strictly adhered to. Forty-two healthy male volunteers will be distributed into acupoints electroacupuncture (AE) group, non-acupoints electroacupuncture (NAE) control group, or blank control group. This trial will comprise 1-week baseline (baseline sleep), 1-week preventative treatment, 30-h total sleep deprivation (TSD), and 24-h after waking follow-up period. Participants in the AE group and the NAE control group during the preventative treatment period will be administered with EA treatment once daily for 1 week. Participants in the blank control group will not be administered with any treatment. The primary outcome will be the Profile of Mood States (POMS) Scale. Secondary outcome measures will include changes in the Noldus FaceReader (a tool for automatic analysis of facial expressions) and Positive and Negative Affect Schedule (PANAS) Scale. Total sleep deprivation will be 30 h. During the 30-h TSD period, participants will be subjected to 11 sessions of assessment. Adverse events will be recorded. DISCUSSION: This study is designed to evaluate the efficacy and safety of EA for the prevention of negative moods after SD. The results of this trial will allow us to compare the effects of EA on mood after SD at different time points. Moreover, the findings from this trial will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chi2000039713 . Registered on 06 November 2020.

Artemisinin elevates ergosterol levels of Candida albicans to synergise with amphotericin B against oral candidiasis.

Oral candidiasis, especially caused by Candida albicans, is the most common fungal infection of the oral cavity. The increase in drug resistance and lack of new antifungal agents call for new strategies of antifungal treatment. This study repurposed artemisinin (Art) as a potentiator to the polyene amphotericin B (AmB) and characterised their synergistic mechanism against C. albicans and oral candidiasis. The synergistic antifungal activity between Art and AmB was identified by the checkerboard and recovery plate assays according to the fractional inhibitory concentration index (FICI). Art showed no antifungal activity even at >200 mg/L. However, it significantly reduced AmB dosages against the wild-type strain and 75 clinical isolates of C. albicans (FICI ≤ 0.5). Art significantly upregulated expression of genes from the ergosterol biosynthesis pathway (ERG1, ERG3, ERG9 and ERG11), as shown by RT-qPCR, and elevated the ergosterol content of Candida cells. Increased ergosterol content significantly enhanced binding between fungal cells and the polyene agent, resulting in sensitisation of C. albicans to AmB. Drug combinations of Art and AmB showed synergistic activity against oral mucosal infection in vivo by reducing the epithelial infection area, fungal burden and inflammatory infiltrates in murine oropharyngeal candidiasis. These findings indicate a novel synergistic antifungal drug combination and a new Art mechanism of action, suggesting that drug repurposing is a clinically practical means of antifungal drug development and treatment of oral candidiasis.

The effects of dietary supplementation with lotus leaf extract on the immune response and intestinal microbiota composition of broiler chickens.

This study aimed to assess the effect of lotus leaf extract (LLE) on the immune response and intestinal microbiota composition of broiler chickens. One-day-old birds were assigned to 7 treatments. Two maize-based control diets were each given with or without 50 mg/kg chlortetracycline (antibiotics and blank control groups, respectively). Five experimental diets were each given with 1.0, 2.5, 5.0, 7.5, or 10.0 g/kg LLE. Average daily weight gain (ADG) was assessed, and the immune organ index was calculated. Serum cytokine and immunoglobulin levels were determined, and intestinal microbiota composition was analyzed via high-throughput sequencing of the 16S rRNA gene. Results showed that in the LLE5 group, ADG was higher than that of the antibiotics and blank control groups (P < 0.05) from d 7 to 21, the thymus index at d14, spleen index at d 21, and bursa index at d 14 and 21 were increased markedly (P < 0.05). In the LLE5 and LLE7.5 groups, serum total IgG and sIgA concentrations were higher than those of the antibiotics and blank control groups (P < 0.05) at d 7 and higher than those of the antibiotics group (P < 0.05) at d 14. No significant effect was observed for interferon-gamma concentrations between the antibiotics and LLE5 or LLE7.5 groups; compared with the antibiotics group, IL2 concentrations were increased in the LLE5 group at d 7 and in the LLE7.5 group at d 21 (P < 0.05). 16s rRNA sequencing analysis revealed that there were 1,704, 232, and 4,814 operational taxonomic unit in the blank control group, antibiotics group, and LLE groups, respectively. The intestinal microbiota consisted mainly of Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes (>95%) at the phylum level; at the family level, the abundance of Clostridiaceae and Bacteroidales S24-7 was increased, whereas that of Peptostreptococcaceae was reduced in LLE5 group (P < 0.05). These findings suggest that LLE may be a good source of prebiotics, helping to modulate the immune response and boost the levels of beneficial bacteria.

Stimuli-responsive drug delivery systems for head and neck cancer therapy.

Head and neck cancer (HNC) is among the most common malignancy that has a profound impact on human health and life quality. The treatment for HNC, especially for the advanced cancer is stage-dependent and in need of combined therapies. Various forms of adjuvant treatments such as chemotherapy, phototherapy, hyperthermia, gene therapy have been included in the HNC therapy. However, there are still restrictions with traditional administration such as limited in situ therapeutic effect, systemic toxicity, drug resistance, etc. In recent years, stimuli-responsive drug delivery systems (DDSs) have attracted the great attention in HNC therapy. These intelligent DDSs could respond to unique tumor microenvironment, external triggers or dual/multi stimulus with more specific drug delivery and release, leading to enhanced treatment efficiency and less reduced side effects. In this article, recent studies on stimuli-responsive DDSs for HNC therapy were summarized, which could respond to endogenous and exogenous triggers including pH, matrix metalloproteinases (MMPs), reactive oxygen species (ROS), redox condition, light, magnetic field and multi stimuli. Their therapeutic remarks, current limits and future prospect for these intelligent DDSs were discussed. Furthermore, multifunctional stimuli-responsive DDSs have also been reviewed. With the modification of drug carriers or co-loading with therapeutic agents. Those intelligent DDSs showed more biofunctions such as combined therapeutic effects or integration of diagnosis and treatment for HNC. It is believed that stimuli-responsive drug delivery systems showed great potential for future clinic translation and application for the treatment of HNC.