Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health.

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson's and Alzheimer's diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify widespread changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide a holistic view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.

Enrichment and health risks associated with trace elements in medicine food homology teas.

Owing to the irreplaceable role of traditional Chinese medicine in the history of human resistance to diseases, medicine food homology teas (MFHTs) have emerged as a widely-consumed daily drink, although they may contain toxic or excessive trace elements. This study aims to determine the total and infused concentrations of nine trace elements (Fe, Mn, Zn, Cd, Cr, Cu, As, Pb, and Ni) in 12 MFHTs collected from 18 provinces in China, to evaluate their potential risks to human health, and to explore the factors affecting the trace element enrichment in traditional MFHTs. The exceedances of Cr (82%) and Ni (100%) in 12 MFHTs were higher than those of Cu (32%), Cd (23%), Pb (12%), and As (10%). The high values of the Nemerow integrated pollution index of dandelions and Flos sophorae (25.96 and 9.06, respectively) indicate severe trace metal pollution. The health risk assessment results showed that As, Cr, and Mn in the 12 types of MFHTs posed high non-carcinogenic risk. Honeysuckle and dandelion teas may be hazardous to human health through trace element exposure when consumed daily. The enrichment of Cr, Fe, Ni, Cu, Zn, Mn, and Pb in MFHTs is influenced by the MFHT type and producing area, whereas As and Cd are mainly controlled by the MFHT type. Environmental factors such as soil background values, rainfall, and temperature also affect the enrichment of trace elements in MFHTs collected from different producing areas.

Trait Mindfulness and Problematic Smartphone Use in Chinese Early Adolescent: The Multiple Mediating Roles of Negative Affectivity and Fear of Missing Out.

This study used a cross-sectional study design to investigate whether the mindfulness trait was a protective factor against problematic smartphone use (PSPU) of early adolescents, and whether negative affectivity and fear of missing out (FoMO) mediated this relationship. The study selected a sample of middle school students (N = 517, 46.03% males, Mage = 13.81, SD = 1.40) in China. The results of the structural equation modelling indicated that (a) mindfulness significantly and negatively predicted PSPU, (b) FoMO played a mediating role between mindfulness and PSPU, (c) negative affectivity (including depression and anxiety) played a mediating role between mindfulness and PSPU, but loneliness did not, and (d) negative affectivity and FoMO played a chain-mediated role, and depression, anxiety, and loneliness played a chain-mediated role with FoMO between mindfulness and PSPU. We discuss the possibility that high levels of mindfulness in early adolescents may reduce the short-term effects of problematic smartphone use by reducing negative emotions and FoMO and relate our results to an emphasis on the role of enhanced mindfulness in long-term internal self-regulation and well-being. Findings have implications for individuals and schools for PSPU prevention and intervention.

Wheelchair Tai Chi Ball Exercise for Improving Neuromuscular Functions of Older Adults With Disability.

The purposes of this perspective article were to summarize Wheelchair or Seated Tai Chi studies related to neuromuscular functions of older adults with disability; to describe the development of Wheelchair Tai Chi Ball (WTCB) exercise - a concept to combine mind-body exercise with strength training; and to propose a new Telehealth WTCB exercise for improving neuromuscular functions of old adults with spinal cord injury (SCI) and disability. With reference to neuromuscular functions, WTC intervention may have positive effects on simple reaction time, range of motion at the shoulder and trunk, static and dynamic sitting balance, handgrip strength, vagal activity, and sympathetic activity among older adults with disability. The developed WTCB intervention is a feasible and safe exercise which combines the mind-body exercise and strength conditioning into one exercise which possesses aerobic, stretching and strength trainings and may facilitate neuromuscular functions of older adults with disability. The proposed Telehealth WTCB 12 forms (TWTCB12) exercise with a "Moving Shadow" method in the telehealth may enable the learner to superimpose learner's image on an expert's demonstrating model to enhance the learning and practice effects. Since wheelchair users will learn and practice TWTCB12 movements in a seated position or sitting on a wheelchair the "Moving shadow" method on Zoom would provide an ideal telehealth learning and practice environment for the wheelchair users to learn and practice TWTCB12 exercise from home more feasible and user friendly.

Characterization of the Key Aroma Compounds of Three Kinds of Chinese Representative Black Tea and Elucidation of the Perceptual Interactions of Methyl Salicylate and Floral Odorants.

Jinjunmei (JJM), Keemun (KM), and Dianhong (DH) are the representative black teas in China, and they have always been favored by consumers. In this study, we aim to obtain the aroma characteristic information of volatile components in black tea samples through headspace solid-phase microextraction (HS-SPME), solvent-assisted flavor evaporation (SAFE), and gas chromatography-mass spectrometry combined with gas chromatography-olfactometry technology. The results showed that 70 compounds including α-methylbenzyl alcohol (isomer of ß-phenylethanol) were identified as odorants. Among them, 39 compounds such as linalool and geraniol showed a high degree of aroma contribution. Furthermore, the Feller's additive model was used to explore the perceptual interactions among the methyl salicylate and the floral compounds (10 groups): five groups of binary compounds showed masking effect after mixing, one group showed additive effect, and four groups showed synergistic effect. The ratio (R) was compared with the aroma index (n) of Steven's law, which found a high-fitness exponential relationship. The results of this study help to provide additional and new theoretical guidance for improving the aroma quality of black tea.

Mechanisms and Molecular Targets of BuShenHuoXue Formula for Osteoarthritis.

The aim was to identify latent mechanism of BuShenHuoXue (BSHX) formula for the management of osteoarthritis (OA) through the network pharmacology approach and experimental validation. We obtained OA-related targets through the Gene Expression Omnibus database and bioactive ingredients with corresponding targets in the formula via the Traditional Chinese Medicine Systems Pharmacology database. Subsequently, networks of the protein-protein interaction and compound-disease target were created and enrichment analysis was implemented. Furthermore, in vitro, IL-1ß was applied to rat chondrocytes to mediate apoptosis through inflammation and the Alcian blue and type II collagen staining was used to observe cell morphology. The TUNEL and DAPI staining was performed to observe chondrocyte apoptosis, and the apoptosis rates were gauged via flow cytometry. In addition, we utilized Western blot and PCR to detect the protein and mRNA expression, respectively. A total of 104 potential chemicals and 42 intersecting targets were screened out. Quercetin and luteolin from BSHX formula were principal ingredients. The experiment validated quercetin might suppress chondrocyte apoptosis mediated by IL-1ß and reduce SELE, MMP2, and COL1 expression. Via the AGE-RAGE signaling pathway in diabetic complications, quercetin could aim at SELE, MMP2, and COL1 and exert antagonistic effects against OA.

Adenosine receptor A2B mediates alcoholic hepatitis by regulating cAMP levels and the NF-KB pathway.

Alcoholic hepatitis is a serious form of liver damage. Inflammation is a key factor in alcoholic hepatitis and plays a key role in the progression of alcoholic liver disease. Adenosine receptor A2B (A2BAR) is a member of the adenosine receptor family and generally considered to be a negative regulator of the inflammatory response. We found that A2BAR was the most highly expressed adenosine receptor in ETOH-fed mouse liver tissue and was also highly expressed in primary Kupffer cells and ETOH-induced RAW264.7 cells. In addition, injection of BAY 60-6583 stimulated A2BAR, induced upregulation of the expression levels of cAMP, and reduced ETOH-induced steatosis and inflammation in mice. At the same time, knockdown of A2BAR in vitro increased the inflammatory response in RAW264.7 cells triggered by ETOH. After knockdown of A2BAR in vitro, the release of the inflammatory cytokines IL-6, IL-1ß and TNF-α was increased. After overexpression of A2BAR in vitro, the cAMP level was significantly increased, PKA expression was increased, the expression of phosphorylated proteins in the NF-kB signal transduction pathway was significantly affected, and the expression of the key phosphorylated protein p-P65 was decreased. However, after the simultaneous overexpression of A2BAR and inhibition of PKA, the expression of the key phosphorylated protein p-P65 was still significantly decreased. In addition, after the expression of A2BAR increased or decreased in RAW264.7 cells, AML-12 cells were cultured in the supernatant of RAW264.7 cells stimulated by ETOH, and the apoptosis rate was significantly changed by flow cytometry. These results suggest that A2BAR can reduce alcoholic steatohepatitis by upregulating cAMP levels and negatively regulating the NF-kB pathway. Overall, these findings suggest the significance of A2BAR-mediated inflammation in alcoholic liver disease.

Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway.

BACKGROUND: Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammatory cytokines such as TNF-α or IL-6 are involved in the induction of skeletal muscle atrophy and fat depletion in patients with cancer cachexia. PURPOSE: In this study, we assessed the therapeutic effects of the natural compound alantolactone (AL) on cancer cachexia and tried to clarify the mechanisms by which it ameliorates muscle atrophy. METHODS: The C26 tumor-bearing cancer cachexia mouse model was used to evaluate the efficacy of AL in alleviating cancer cachexia in vivo. The levels of IL-6 or TNF-α in mouse serum were detected using ELISA kits. Cultured C2C12 myotubes and 3T3-L1 adipocytes treated with conditioned medium of C26 tumor cells, IL-6 or TNF-α were employed as in vitro cancer cachexia models to examine the effects of AL in vitro. RESULTS: AL (5 or 10 mg/kg, qd, i.p.) protected mice with C26 tumors and cachexia from a loss of body weight and muscle wasting but only slightly ameliorated fat loss. The circulating level of IL-6 but not TNF-α was significantly decreased by AL. AL treatment significantly inhibited STAT3 activation in the gastrocnemius (GAS) muscle of cancer cachexia mice. AL (0.125, 0.25, 0.5 and 1 µM) dose-dependently ameliorated myotube atrophy and STAT3 activation in cultured C2C12 myotubes induced by conditioned medium from C26 tumor cells. AL also ameliorated C2C12 myotube atrophy induced by IL-6 and inhibited IL-6-mediated STAT3 activation. AL exhibited weak effects on ameliorating TNF-α-mediated myotube atrophy and NF-κB activation. Only AL at high doses of more than 5 µM ameliorated lipolysis and STAT3 activation induced in mature 3T3-L1 adipocytes by conditioned medium from C26 tumor cells. CONCLUSIONS: AL significantly ameliorated muscle atrophy in a cancer cachexia model mainly through the inhibition of the STAT3 pathway. AL might be a promising lead compound in the development of drug candidates for cancer cachexia therapy.

Diagnosis of TCM symptoms and analysis of risk factors of mild cognitive impairment in patients with type 2 diabetes mellitus.

OBJECTIVE: To explore the diagnosis of traditional Chinese medicine (TCM) syndrome and analyze the risk factors of mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM). METHODS: 141 T2DM patients, who were hospitalized in department of endocrinology of our hospital from February 2020 to December 2020, were chosen as research subjects. The patients were divided into an observation group (n=65, T2DM with MCI) and a control group (n=76, T2DM with normal cognitive function) according to the Montreal Cognitive Assessment (MoCA) score and diagnostic criteria of MCI. Pearson correlation analysis was used to study the correlation between MoCA score and influencing factors, and multiple logistic regression analyses were applied to analyze the risk factors of T2DM patients. RESULTS: Deficiency of kidney essence (34/65, 52.31%) and phlegm obstructing orifices (16/65, 2.62%) were common in T2DM patients with MCI. The observation group had apparently lower MoCA scores than the control group (23.46±3.12 points vs. 27.39±2.56 points, t=8.2150, P=0.0000). According to the results of multivariate logistic regression analysis, age, course of diabetes, homocysteine (HCY) and glycosylated hemoglobin (HbAlc) were the independent risk factors of MCI, and the education level was a protective factor. CONCLUSION: Mental deficiency and phlegm obstruction are common in T2DM patients complicated with MCI. The factors such as age, diabetes course, education degree, HCY and HbAlc are closely related to MCI. The occurrence of MCI in T2DM patients can be prevented by improving the education degree of patients, effective control of blood glucose and reduction of HCY level.

ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus-pituitary-thyroid axis in male mice.

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

Vitamin B1 Intake and the Risk of Colorectal Cancer: a Systematic Review of Observational Studies.

Colorectal cancer is the main leading cause of death from cancer worldwide. Protective effects of vitamin B1 on colorectal cancer have been observed in some epidemiological studies. A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B1 with the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to September 2020). We extracted data from articles on vitamin B1 and used a multivariable-adjusted odds ratio (OR) and a random-effects model for analysis. We found seven articles meeting the inclusion criteria (1 of cohort studies and 6 case-control studies) and a total of 6,184 colorectal cancer cases were included in this meta-analysis. The multivariable-adjusted OR for pooled studies for the association of roughly the same high dose level versus the lowest vitamin B1 intake and the risk of colorectal cancer was 0.76 (95% confidence interval ([95%CI]: 0.65, 0.89). This meta-analysis studied the relationship between vitamin B1 and colorectal cancer. We found vitamin B1 intake was inversely associated with the risk of colorectal cancer. However, further research and large sample studies need to be conducted to better validate the result.

Anti-adipogenicadamantane type polycyclic polyprenylated acylphloroglucinols from Hypericum subsessile.

Hypersubones D-H (1-5), five new polycyclic polyprenylated acylphloroglucinols (PPAPs) type metabolites with intriguing adamantane and homo-adamantane skeletons, were characterized from aerial parts of Hypericum subsessile. Compounds 1-2 were elucidated to share an adamantane core with 28,29-expoxide moiety, while 3-5 were homo-adamantane type PPAPs sharing a1,2-dioxepane ring system. Their structures were determined on the basis of comprehensive NMR and MS spectroscopic data.The anti-adipogenesis activities of these isolates were evaluated through employing 3T3-L1 cells as an in vitro system using oil red O staining, and compounds 1, 2 and 5 were able to significant inhibit the adipocyte differentiation, which implied that these compounds possessed anti-adipogenic activity.

Development of a Simple In Vitro Assay To Identify and Evaluate Nucleotide Analogs against SARS-CoV-2 RNA-Dependent RNA Polymerase.

Nucleotide analogs targeting viral RNA polymerase have been proved to be an effective strategy for antiviral treatment and are promising antiviral drugs to combat the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we developed a robust in vitro nonradioactive primer extension assay to quantitatively evaluate the efficiency of incorporation of nucleotide analogs by SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Our results show that many nucleotide analogs can be incorporated into RNA by SARS-CoV-2 RdRp and that the incorporation of some of them leads to chain termination. The discrimination values of nucleotide analogs over those of natural nucleotides were measured to evaluate the incorporation efficiency of nucleotide analog by SARS-CoV-2 RdRp. In agreement with the data published in the literature, we found that the incorporation efficiency of remdesivir-TP is higher than that of ATP and incorporation of remdesivir-TP caused delayed chain termination, which can be overcome by higher concentrations of the next nucleotide to be incorporated. Our data also showed that the delayed chain termination pattern caused by remdesivir-TP incorporation is different for different template sequences. Multiple incorporations of remdesivir-TP caused chain termination under our assay conditions. Incorporation of sofosbuvir-TP is very low, suggesting that sofosbuvir may not be very effective in treating SARS-CoV-2 infection. As a comparison, 2'-C-methyl-GTP can be incorporated into RNA efficiently, and the derivative of 2'-C-methyl-GTP may have therapeutic application in treating SARS-CoV-2 infection. This report provides a simple screening method that should be useful for evaluating nucleotide-based drugs targeting SARS-CoV-2 RdRp and for studying the mechanism of action of selected nucleotide analogs.

Steaming Changes the Composition of Saponins of Panax notoginseng (Burk.) F.H. Chen That Function in Treatment of Hyperlipidemia and Obesity.

Saponins of Panax notoginseng (Burk.) F.H. Chen have been classified as a type of composition in functional foods for numerous diseases. However, its mild effects and other characteristics limited clinical applications in diseases. Inspired by "nine steaming and nine processing" of P. notoginseng in traditional Chinese medicine, we developed a "steaming"-mimic protocol, which significantly changed the composition of saponins of P. notoginseng from the original, R1, Rg1, Re, Rb1, and Rd (raw-PNS), to the products after steaming, 20S/R-Rh1, Rk3, Rh4, 20S/R-Rg3, Rk1, and Rg5 (N-PNS). Surprisingly, N-PNS demonstrated promising activities in improving hyperlipidemia and reducing body weight and weight of white adipose tissue and the inhibition of adipogenesis in obese mice. In accordance with the results in vivo, N-PNS remarkably blunted adipogenesis at the early stage of differentiation dose-dependently in vitro. Moreover, we demonstrated that the activity may involve the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway by promoting phosphorylation of AMPKT172 and downregulating its downstream factors: sterol regulatory element binding protein 1c, stearoyl-CoA desaturase 1, and fatty acid synthase. Taken together, the steaming-induced eight compositions of saponins showed a very promising function in improving hyperlipidemia and obesity both in vivo and in vitro, providing fundamental evidence for future study and application in treatment of hyperlipidemia, obesity, and other lipid-related metabolic syndromes.

The Prognostic Value of Autophagy-Related Markers Bclin-1 and LC-3 in Colorectal Cancers: A Systematic Review and Meta-analysis.

OBJECTIVE: At present, the relationship between autophagosomes and the prognosis of various cancers has become a subject of active investigation. A series of studies have demonstrated the correlation between autophagy microtubule-associated protein light chain 3 (LC-3), Beclin-1, and colorectal cancer (CRC). Since autophagy has dual regulatory roles in tumors, the results of this correlation are also uncertain. Hence, we summarized the relationship between Beclin-1, LC-3, and CRC using systematic reviews and meta-analysis to clarify their prognostic significance in it. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched online up to April 1, 2019. The quality of the involving studies was assessed against the Newcastle-Ottawa Scale (NOS). Pooled hazard ratio (HR) and 95% confidence interval (CI) in a fixed or random effects model were used to assess the strength of correlation between Beclin-1, LC-3, and CRC. RESULTS: A total of 9 articles were collected, involving 2,297 patients. Most literatures scored more than 6 points, suggesting that the quality of our including research was acceptable. Our finding suggested that the expression of Beclin-1 was not associated with overall survival (HR = 0.68, 95% CI (0.31-1.52), P=0.351). Nonetheless, LC-3 expression exerted significant impact on OS (HR = 0.51, 95% CI (0.35-0.74), P < 0.05). Subgroup analysis exhibited that Beclin-1 expression was associated with OS at TNM stage III (HR = 0.04, 95% CI = 0.02-0.08, P < 0.05), surgical treatment (HR = 1.53, 95% CI (1.15-2.02), P=0.003), and comprehensive treatment (HR = 0.27 95% CI (0.08-0.92), P=0.036), respectively. Similarly, the results showed the increased LC-3 expression in CRC was related to OS in multivariate analyses (HR = 0.44, 95% CI (0.34-0.57), P < 0.05), stages (HR = 0.51, 95% CI (0.35-0.74), P < 0.05), and comprehensive treatment (HR = 0.44, 95% CI (0.34-0.57), P < 0.05). CONCLUSIONS: Autophagy-related proteins of LC-3 might be an important marker of CRC progression. However, since the number of the original studies was limited, more well-designed, large-scale, high-quality studies are warranted to provide more convincing and reliable information.

Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I.

Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%-80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg-1per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms.

Application of Herbal Traditional Chinese Medicine in the Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid loss of renal function, which may further develop into chronic kidney damage (CKD) or even end-stage renal disease (ESRD). AKI is a global health problem associated with high morbidity and costly treatments, and there is no specific or effective strategy to treat AKI. In recent years, Traditional Chinese Medicine (TCM) has attracted more attention, with lines of evidence showing that application of TCM improved AKI, and the mechanisms of action for some TCMs have been well illustrated. However, reviews summarizing the progress in this field are still lacking. In this paper, we reviewed TCM preparations and TCM monomers in the treatment of AKI over the last 10 years, describing their renal protective effects and mechanisms of action, including alleviating inflammation, programmed cell death, necrosis, and reactive oxygen species. By focusing on the mechanisms of TCMs to improve renal function, we provide effective complementary evidence to promote the development of TCMs to treat AKI. Moreover, we also summarized TCMs with nephrotoxicity, which provides a more comprehensive understanding of TCMs in the treatment of AKI. This review may provide a theoretical basis for the clinical application of TCMs in the future.

Assessment of the hepatocyte protective effects of gypenoside and its phosphorylated derivative against DHAV-1 infection on duck embryonic hepatocytes.

BACKGROUND: Duck viral hepatitis (DVH) is an acute disease of young ducklings with no effective veterinary drugs for treatment. Gynostemma pentaphyllum is a well-known traditional Chinese medicine that plays an important role in the treatment of various diseases. Gypenoside (GP), one of the main ingredients of Gynostemma pentaphyllum, was reported with good hepatoprotective effects. However, its low solubility limits its application in the clinics. To improve its solubility and bioactivity, a phosphorylated derivative of gypenoside (pGP) was prepared by the sodium trimetaphosphate-sodium tripolyphosphate (STMP-STPP) method. An infrared spectroscopy method was applied to analyse the structures of GP and pGP. Then, a methyl thiazolyl tetrazolium (MTT) colorimetric assay was applied to study the hepatocyte protective efficacy of these two drugs against duck hepatitis A virus type 1 (DHAV-1) infection, and qPCR, TUNEL labelling and flow cytometry methods were used to study the relevant hepatocyte protective in vitro. RESULTS: The infrared spectroscopy detection results showed that the phosphorylation modification of GP was successful. The MTT colorimetric assay results showed that both GP and pGP possessed good hepatocyte protective efficacy in vitro, and pGP performed better than GP when the drug was added before or after virus inoculation. Furthermore, the qPCR results revealed that both drugs could effectively inhibit the adsorption (when adding GP and pGP pre-virus inoculation), replication and release of DHAV-1, and the viral inhibition rate of pGP was greater than that of GP. The subsequent TUNEL labelling and flow cytometry assays showed that both GP and pGP could significantly inhibit duck embryo hepatocyte apoptosis induced by DHAV-1, and the inhibition effect of pGP was much stronger than that of GP. CONCLUSIONS: GP exerts good hepatocyte protective efficacy not only by inhibiting the proliferation of DHAV-1 but also by inhibiting duck embryonic hepatocyte apoptosis induced by DHAV-1, and phosphorylation modification significantly improves the antiviral and the anti-apoptotic effects of GP. Therefore, pGP has the potential to be developed into a novel drug against DHAV-1 infection.

Proteoliposome-based model for screening inhibitors targeting histidine kinase AgrC.

AgrC, as an integral membrane receptor protein with histidine kinase activity, is an important component of the agr quorum-sensing system of Staphylococcus aureus. AgrC acts as a sensor for the recognition of environmental signals and transduction of the signals into the cytoplasm. Therefore, AgrC is considered to be a compelling target for the development of novel quorum-sensing inhibitors. Here, we constructed a proteoliposome-based model for screening inhibitors targeting AgrC by incorporating AgrC into liposomes. We demonstrated that the dissolution state of the liposome was a critical factor in the reconstruction of the AgrC proteoliposome, in which AgrC maintained similar orientation and function as those in natural biological membranes. Two monomers, namely, rhein and aloeemodin, were successfully screened out as inhibitors targeting AgrC by the proteoliposome-based model from 14 traditional Chinese medicine monomers. The inhibitory effects of these compounds on the growth of suspended bacteria was dose dependent, and subinhibitory concentrations of these compounds significantly reduced the expression of three virulence factors (hla, clfA, and clpP), that are regulated by the agr system. The results preliminarily indicated that rhein and aloeemodin can inhibit the agr signaling pathway and also indirectly confirmed the feasibility and effectiveness of the AgrC proteoliposome as a drug screening model.