Development and evaluation of serological screening based on one dried plasma spot for HIV, syphilis, and HCV.

BACKGROUND: In the effort to prevent and control HIV/AIDS, China has established a national sentinel surveillance system. However, some sentinel sites face limitations in environmental resources and accessibility, prompting the exploration of alternative sample strategies. Dried plasma spots (DPS) samples are viewed as promising alternatives to traditional plasma samples due to their advantages, including sample stability, easy storage, and convenient transport. This study aims to develop a method for screening HIV, Treponema pallidum (TP), and Hepatitis C Virus (HCV) using DPS samples and assess their performance. METHODS: Based on existing commercial assay kits, a detection method was established through the optimization of experimental parameters, including the amount of plasma on filter paper, the volume of elution solution applied to dried plasma spots, the size of dried plasma spots, elution solution volume, elution solution components, elution temperature, and elution time. A series of laboratory evaluation panels were constructed for laboratory assessments, including the laboratory basic panel, laboratory interference panel, and laboratory precision panel. Additionally, clinical samples were used for evaluation. RESULTS: Optimal conditions for DPS sample extraction were: plasma volume, 100 µL; DPS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 2 h; elution temperature, room temperature. A total of 619 paired plasma/DPS samples were tested by both methods. The DPS-based ELISA method exhibited 100% sensitivity/specificity for HIV, 98.6%/100% for TP, and 99.6%/100% for HCV. Kappa values between the plasma samples and DPS samples were 100% for HIV, 99% for TP, and 100% for HCV. The DPS-based ELISA method failed to detect 1 HCV mono-infected sample and TP in 1 HIV/HCV/TP co-infected sample. For the HIV/HCV/TP co-infected sample, the S/CO in the plasma sample was 2.143 and in the DPS sample was 0.5. For HCV, the S/CO (sample OD/cut-off) was 3.049 in the plasma sample and 0.878 in the DPS sample. CONCLUSIONS: A single DPS, following one-time standardized processing, can be used to detect HIV, HCV, and TP. Researching and establishing laboratory testing methods better suited for China's sentinel surveillance have significant practical applications in improving HIV testing in resource-constrained environments.

MiR-421 regulates goat intramuscular preadipocytes differentiation via targeting FGF13.

As a member of the MicroRNA s (miRNAs) family, miR-421 has been widely studied in regulating the proliferation and apoptosis of cancer cells a. However, there are still no reports on miR-421 in regulating adipocyte differentiation and its related mechanisms. Accordingly, this study aimed to investigate the potential involvement of miR-421 in goat intramuscular preadipocytes (P_IMA). The expression level of miR-421 was measured via quantitative real-time PCR during goat P_IMA differentiation. And the effects of miR-421 on goat P_IMA differentiation were studied by liposome transfection, Oil red O staining and qRT-PCR. Furthermore, the miR-421 target was searched and the underlying mechanism was clarified by luciferase reporter assay and rescue experiment. Our results showed that inhibition of miR-421 could accumulation of lipid droplets by upregulation the expression level of AP2, LPL, C/EBPα and SREBP1. Further studies showed that fibroblast growth factor 13 (FGF13) was the direct target of miR-421. Knocking down of FGF13 expression could inhibit lipid droplet formation and down-regulated the expression of key adipogenic regulatory genes. In addition, the rescue experiment revealed that FGF13 is involved in miR-421-induced differentiation of goat P_IMA as a key factor. Overall, these findings indicate that miR-421 is a negative regulator in the progression of differentiation of goat P_IMA by inhibiting the expression of FGF13.

Molecular characterization, expression analysis of Chemerin gene and its potential role in intramuscular adipocyte differentiation of goat.

Chemerin is a cytokine secreted by adipose cells and plays an important regulatory role in adipocyte differentiation and lipid metabolism. However, the function of Chemerin on intramuscular fat (IMF) deposition is still unknown in goat. Here, we cloned the cDNA of goat Chemerin gene using quantitative real-time PCR (qRT-PCR) technique and further clarified the expression pattern of Chemerin in various tissues of goat. The siRNA against Chemerin were synthesized to explore the potential role in intramuscular preadipocyte differentiation of goat. Our results showed that the full-length open reading frame (ORF) of Chemerin was 489 bp encoding 162 amino acids, mainly expressed in liver and Kidney. The interference of Chemerin significantly inhibited the differentiation of goat intramuscular preadipocyte and down-regulated significantly the expression levels of adipogenic marker genes LPL, AP2, SREBP1, PPARγ, C/EBPα, and C/EBPß. These data suggest that Chemerin is a positive regulator of lipogenesis in goat intramuscular preadipocytes. Interestingly, the temporal expression pattern of Chemerin was similar to CMKLR1 during preadipocytre differentiation. These results will facilitate the research on the action of Chemerin gene in goat intramuscular fat deposition.

Preparation methods, structural characteristics, and biological activity of polysaccharides from Platycodon grandiflorus.

Platycodon grandiflorus (P. grandiflorus), a traditional Chinese medicinal herb used for both medicine and food, has a long history of treating respiratory infections, bronchitis, pneumonia, and other lung-related diseases. The therapeutic effects of P. grandiflorus are attributed to its chemical components, including polysaccharides. Among these components, Platycodon grandiflorus polysaccharides (PGP) are recognized as one of the most important and abundant active ingredients, exhibiting various biological activities such as prebiotic, antioxidant, antiviral, anticancer, antiangiogenic, and immune regulatory properties. Incorporating the principles of traditional Chinese medicine, carrier concepts, and modern targeted drug delivery technologies, PGP can influence the target sites and therapeutic effects of other drugs while also serving as a drug carrier for targeted and precise treatments. Therefore, it is essential to provide a comprehensive review of the extraction, separation, purification, physicochemical properties, and biological activities of PGP. In the future, by integrating new concepts, technologies, and processes, further references and guidance can be provided for the comprehensive development of PGP. This will contribute to the advancement of P. grandiflorus in various fields such as pharmaceuticals, health products, and food.

Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored. METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice. RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1ß, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota. CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.

Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway.

BACKGROUND: Lead (Pb) exposure is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin (QE) in diets exerts the nephroprotective effects. This study investigated the effects of quercetin on renal oxidative stress and inflammation in rats exposed to Pb. METHODS: Wistar rats were divided into normal, lead exposure groups, lead plus quercetin groups and quercetin groups. Rats were exposed to lead acetate in the drinking water (500mgPb/L) with or without quercetin co-administration (25 and 50mgQU/kg intragastrically once daily). After 75days, serum uric acid, urea, creatinine, renal reactive oxygen species (ROS) production, thiobarbituric acid reactive substances (TBARS) and histopathological analysis were performed. Pb content in kidney was also assayed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), the extracellular-receptor kinases (ERK1/2), the c-Jun N-terminal kinases (JNK1/2), p38 MAPK and nuclear factor-κB (NF-κB) were measured. RESULTS: Quercetin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators and histopathological analysis. Quercetin significantly decreased Pb content in kidney. Pb-induced profound elevations of oxidative stress in kidney were suppressed by quercetin. Furthermore, quercetin significantly inhibited Pb-induced inflammation in rat kidney. CONCLUSIONS: These results suggest that quercetin has the nephroprotective actions. The inhibition of Pb-induced kidney inflammation by quercetin is due at least in part to its anti-oxidant activity and its ability to modulate the MAPK and NF-κB signaling pathway. GENERAL SIGNIFICANCE: Quercetin might be a potent nephroprotective drug to protect Pb-induced kidney injury.

Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.

Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.

Phytochemicals, Biological Activities, Molecular Mechanisms, and Future Prospects of Plantago asiatica L.

Plantago asiatica L. has been used as a vegetable and nutritious food in Asia for thousands of years. According to recent phytochemical and pharmacological research, the active compositions of the plant contribute to various health benefits, such as antioxidant, anti-inflammatory, antibacterial, antiviral, and anticancer. This article reviews the 87 components of the plant and their structures, as well as their biological activities and molecular research progress, in detail. This review provides valuable reference material for further study, production, and application of P. asiatica, as well as its components in functional foods and therapeutic agents.

A Novel Synbiotic Alleviates Autoimmune Hepatitis by Modulating the Gut Microbiota-Liver Axis and Inhibiting the Hepatic TLR4/NF-κB/NLRP3 Signaling Pathway.

Autoimmune hepatitis (AIH) is a liver disease characterized by chronic liver inflammation. The intestinal barrier and microbiome play critical roles in AIH progression. AIH treatment remains challenging because first-line drugs have limited efficacy and many side effects. Thus, there is growing interest in developing synbiotic therapies. This study investigated the effects of a novel synbiotic in an AIH mouse model. We found that this synbiotic (Syn) ameliorated liver injury and improved liver function by reducing hepatic inflammation and pyroptosis. The Syn reversed gut dysbiosis, as indicated by an increase in beneficial bacteria (e.g., Rikenella and Alistipes) and a decrease in potentially harmful bacteria (e.g., Escherichia-Shigella) and lipopolysaccharide (LPS)-bearing Gram-negative bacterial levels. The Syn maintained intestinal barrier integrity, reduced LPS, and inhibited the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathway. In addition, microbiome phenotype prediction by BugBase and bacterial functional potential prediction using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed that Syn improved gut microbiota function involving inflammatory injury, metabolism, immune response, and pathopoiesia. Furthermore, the new Syn was as effective as prednisone against AIH. Therefore, this novel Syn could be a candidate drug for alleviating AIH through its anti-inflammatory and antipyroptosis properties that relieve endothelial dysfunction and gut dysbiosis. IMPORTANCE Synbiotics can ameliorate liver injury and improve liver function by reducing hepatic inflammation and pyroptosis. Our data indicate that our new Syn not only reverses gut dysbiosis by increasing beneficial bacteria and decreasing lipopolysaccharide (LPS)-bearing Gram-negative bacteria but also maintains intestinal barrier integrity. Thus, its mechanism might be associated with modulating gut microbiota composition and intestinal barrier function by inhibiting the TLR4/NF-κB/NLRP3/pyroptosis signaling pathway in the liver. This Syn is as effective as prednisone in treating AIH without side effects. Based on these findings, this novel Syn represents a potential therapeutic agent for AIH in clinical practice.

A Newly Synbiotic Combination Alleviates Obesity by Modulating the Gut Microbiota-Fat Axis and Inhibiting the Hepatic TLR4/NF-κB Signaling Pathway.

SCOPE: Obesity has been recognized as a worldwide public health crisis, this is accompanied by dysregulation of the intestinal microbiota and upregulation of liver steatosis and adipose inflammation. Synbiotic as a novel alternative therapy for obesity have recently gained much attention. METHODS: This study innovatively research the anti-obesity properties of a newly synbiotic composed of Lactobacillus acidophilus, Bifidobacterium infantis and konjac glucomannan oligosaccharides. RESULTS: The synbiotic treatment can reduce body weight, fat mass, blood sugar, liver steatosis and adipose inflammation in obesity mice fed by high-fat diet (HFD). Meanwhile, synbiotic treatment activated brown adipose tissue and improve energy, glucose and lipid metabolism. In addition, synbiotic treatment not solely enhanced the protection of intestinal barrier, but also ameliorated gut microbiota dysbiosis directly by enhancing beneficial microbes and reducing potentially harmful bacteria. Furthermore, the microbiome phenotype and functional prediction showed that synbiotic treatment can improve the gut microbiota functions involving inflammatory state, immune response, metabolism and pathopoiesia. CONCLUSION: The synbiotic may be an effective candidate treatment strategy for the clinical prevention and treatment of obesity and other associated metabolic diseases such as hyperlipidemia, nonalcoholic fatty liver diseases by alleviating inflammatory response, regulating energy metabolism and maintaining the balance of intestinal microecology.

Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. However, its protective effects against lead (Pb) induced injury in kidney have not been clarified. The aim of the present study was to investigate the effects of puerarin on renal oxidative stress and apoptosis in rats exposed to Pb. Wistar rats were exposed to lead acetate in the drinking water (500mg Pb/l) with or without puerarin co-administration (100, 200, 300 and 400mg PU/kg intragastrically once daily) for 75days. Our data showed that puerarin significantly prevented Pb-induced nephrotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of kidney damage (serum urea, uric acid and creatinine) and histopathological analysis. Moreover, Pb-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of intracellular reduced glutathione (GSH) level in kidney, were suppressed by treatment with puerarin. Furthermore, TUNEL assay showed that Pb-induced apoptosis in rat kidney was significantly inhibited by puerarin. In exploring the underlying mechanisms of puerarin action, we found that activities of caspase-3 were markedly inhibited by the treatment of puerarin in the kidney of Pb-treated rats. Puerarin increased phosphorylated Akt, phosphorylated eNOS and NO levels in kidney, which in turn inactivated pro-apoptotic signaling events including inhibition of mitochondria cytochrome c release and restoration of the balance between pro- and anti-apoptotic Bcl-2 proteins in kidney of Pb-treated rats. In conclusion, these results suggested that the inhibition of Pb-induced apoptosis by puerarin is due at least in part to its antioxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.

Cellular and molecular mechanisms of the Ganoderma applanatum extracts induces apoptosis on SGC-7901 gastric cancer cells.

To investigate the inhibition effect of Ganoderma applanatum extract (GAEAE) on human gastric cancer cell lines and apoptosis mechanism, Alamar Blue assay was used to assess the inhibition and apoptosis-inducing effect of the GAEAE on proliferation of SGC-7901 cells, the DNA ladders of the apoptosis cells was done, the mRNA expression of p53, Bax, Bcl-2 and JNK were analysed by reverse transcription-polymerase chain reaction. The levels of the Cyt C and the p53, Bax/Bcl-2, JNK proteins and the caspase-3 activity in the SGC-7901 cells were measured with ELISA kits. Our data showed that the GAEAE markedly inhibited the proliferation of SGC-7901 cells in a dose-dependent manner. The expression of Bcl-2 protein was down-regulated and Bax, c-jun, p53 protein expressions were up-regulated by the GAEAE treatment in SGC-7901 cells. The activity of caspase-3 was markedly increased and the Cty C was markedly released into cytoplasm from the mitochondria after GAEAE action. In conclusion, our results indicated that the GAEAE could enhance the sensitivity of SGC-7901 cells to the c-jun, p53, Bax and Bcl-2 induced apoptosis and provided a promising approach to anti-human gastric cancer therapy with Ganoderma applanatum.

Anti-oxidant, anti-inflammatory and anti-fibrosis effects of ganoderic acid A on carbon tetrachloride induced nephrotoxicity by regulating the Trx/TrxR and JAK/ROCK pathway.

Ganoderic acid A (GAA), one of the major triterpenoid components extracted from Ganoderma mushroom has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of GAA on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. The male mice were treated with 25 and 50 mg/mg GAA after stimulated with CCl4. Our results showed that GAA improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. GAA ameliorated CCl4-induced indices of inflammation. GAA suppressed oxidative stress by regulating the glutathione antioxidant system and the thioredoxin antioxidant system. GAA increased the activations of thioredoxin reductase (TrxR), Trx, GSH, SOD, GPx. Furthermore, GAA supplementation inhibited the JAK and STAT3 pathway. GAA inhibited the activations of RhoA, ROCK, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that GAA possesses immune-protective properties through regulating the Trx/TrxR, JAK2/STAT3 and RhoA/ROCK pathways.

MiR-26b-5p regulates the preadipocyte differentiation by targeting FGF21 in goats.

MicroRNAs are a class of highly conserved and widely distributed non-coding RNAs. It is known that miR-26b has a high abundance in adipose tissue and is considered to be an effective regulator of adipogenesis. However, it is unclear whether miR-26b-5p, the product of miR-26b precursor, has the same effect as miR-26b. In the present study, we explored the potential role of miR-26b-5p in preadipocyte differentiation of goats. We found that the expression of miR-26b-5p had dramatic change during goat intramuscular preadipocyte differentiation. Transfection and RT-qPCR revealed that overexpression of miR-26b-5p increased the level of adipogenic marker genes and lipid accumulation in goat preadipocyte, suggesting that miR-26b-5p positively regulates goat preadipocyte differentiation. Furthermore, bioinformatics analysis and dual fluorescein reporter assays were performed to predict and validate the targets of miR-26b-5p. The results showed that miR-26b-5p has a binding site in the 3'UTR of FGF21 and overexpression of miR-26b-5p significantly down-regulated the expression of FGF21 mRNA. Luciferase activity assays confirmed that miR-26b-5p is a positive regulator of goat intramuscular preadipocyte via targeting FGF21. These findings provide reference for further revealing of the regulatory networks of goat fat metabolism and contribute to a better understanding of intramuscular fat deposition in goats.

Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-ß1/Smad3 pathway.

Bixin, an natural carotenoid extracted from the seeds of the Bixa orellana has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of Bixin on carbon tetrachloride (CCl4)-induced kidney inflammation, fibrosis and oxidative stress in mice. Our results showed that Bixin improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. Bixin ameliorated CCl4-induced inflammation in kidneys by reducing the levels of TNF-α and IL-1ß. Bixin suppressed oxidative stress by decreasing the MDA level and increasing the activation of SOD, CAT and GPx. Furthermore, Bixin increased the levels of PPAR-γ, NQO1, HO-1 and the nuclear translocation of Nrf2 in the kidneys of mice. Bixin supplementation inhibited the activation of TLR4, MyD88, NF-κB, TGF-ß and Smad3. Thus, this study demonstrated that Bixin possesses anti-oxidant, anti-inflammatory and anti-fibrosis properties through regulating the Nrf2/TLR4/MyD88 and PPAR-γ/TGF-ß1/Smad3 pathways.

An efficient method for simultaneously screening for HIV, syphilis, and HCV based on one dried blood spot sample.

OBJECTIVE: The aim of this study was to optimize the parameters of a dried blood spot (DBS)-based ELISA method to simultaneously screen for anti-HIV, anti-hepatitis C virus (HCV) and anti-treponema pallidum (TP) antibodies, and investigate the assay performance. METHODS: Experiments were performed to establish optimized parameters for a DBS-based ELISA method to simultaneously screen for anti-HIV, anti-HCV, and anti-TP antibodies. Then, 429 paired plasma and DBS samples were collected to evaluate the performance of the assay with optimized parameters. Plasma test results were used as the reference standard. RESULTS: The optimized assay conditions were: blood volume, 70-100 µL; DBS size, whole spot; eluent volume, 500 µL; eluent, PBS with 1‰ Tween20; elution time, 4 h; elution temperature, room temperature. The overall prevalence of HIV, HCV, and TP was 6.06% (95% confidence interval [CI]: 4.07-8.87%), 27.74% (95% CI: 23.60-32.28%), and 14.92% (95% CI: 11.75-18.73%). The clinical sensitivity of the assay for anti-HIV, anti-HCV, and anti-TP antibodies was 88.46%, 98.32%, and 92.19%, respectively. The assay was 100% specificity for each analyte. The assay positive predictive value for each analyte was 100%, and the negative predictive values were >98%. Of the 429 samples, 9 DBS results were different than the plasma results; in these samples the plasma signal-to-cutoff rations were low (range, 1.40-7.81). CONCLUSION: The DBS-based ELISA method demonstrated good performance for simultaneously screening for anti-HIV, anti-HCV, and anti-TP antibodies. DBS samples are a promising method to screen for HIV, HCV, and TP infections. IMPORTANCE: DBS samples are a promising alternative to plasma samples, with the advantages of good sample stability, smaller blood volume, simpler storage, and easier transport. DBS sample testing is used for the diagnosis of a wide variety of pathogens, including HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV). The performance of DBS samples for the serological diagnosis of HIV, HCV, and Treponema pallidum (TP) has been demonstrated to be good in many studies, and therefore DBS is regarded as an ideal choice to screen for HIV, HCV, and TP infections, especially in difficult-access or resource-limited settings. There is no generally accepted procedure for sample collection and processing of DBS samples and there are few studies on simultaneous detection of anti-HIV, anti-HCV and anti-TP using a single DBS.

Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aß). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/ß-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl4)-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl4-induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl4-induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5'-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-ß. Collectively, this study clarified that GAS attenuates CCl4-induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway.

Paediatric cerebral palsy prevalence and high-risk factors in Henan province, Central China.

OBJECTIVE: To evaluate the prevalence of, and risk factors for, cerebral palsy in Henan province, China. METHODS: The prevalence of cerebral palsy in children aged 0-6 years between September 2011 and September 2012 was investigated using a stratified-clustered-random sampling method. An age-, sex- , and residence-matched control group of typically developing children was recruited. Univariate analysis and multinomial logistic regression analysis were used to identify risk factors associated with cerebral palsy. RESULTS: The prevalence of cerebral palsy in Henan province was 2.37 per 1,000 live births. Risk factors included: moving into a newly painted room; complicating maternal diseases (infection, heart disease, hypertension, anaemia, diabetes, kidney disease) during pregnancy; high gravidity (> 3); foetal asphyxia; low birth-weight (< 2,500 g); and hypoxic-ischaemic encephalopathy. CONCLUSION: The prevalence of cerebral palsy in Henan province was 2.37 per 1,000 live births. Parents and clinicians should be aware of the risk factors for cerebral palsy.

Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-ß1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-ß1/Smad3 and autophagy pathway.