Oligomeric proanthocyanidins ameliorates osteoclastogenesis through reducing OPG/RANKL ratio in chicken's embryos.

Skeletal disorders can seriously threaten the health and the performance of poultry, such as tibial dyschondroplasia (TD) and osteoporosis (OP). Oligomeric proanthocyanidins (OPC) are naturally occurring polyphenolic flavonoid compounds that can be used as potential substances to improve the bone health and the growth performance of poultry. Eighty 7-day-old green-eggshell yellow feather layer chickens were randomly divided into 4 groups: basal diet and basal diet supplementation with 25, 50, and 100 mg/kg OPC. The results have indicated that the growth performance and bone parameters of chickens were significantly improved supplementation with OPC in vivo, including the bone volume (BV), the bone mineral density (BMD) and the activities of antioxidative enzymes, but ratio of osteoprotegerin (OPG)/receptor activator of NF-κB (RANK) ligand (RANKL) was decreased. Furthermore, primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes/macrophages (BMMs) were successfully isolated from femur and tibia of chickens, and co-cultured to differentiate into osteoclasts in vitro. The osteogenic differentiation derived from BMSCs was promoted treatment with high concentrations of OPC (10, 20, and 40 µmol/L) groups in vitro, but emerging the inhibition of osteoclastogenesis by increasing the ratio of OPG/RANKL. In contrary, the osteogenic differentiation was also promoted treatment with low concentrations of OPC (2.5, 5, and 10 µmol/L) groups, but osteoclastogenesis was enhanced by decreasing the ratio of OPG/RANKL in vitro. In addition, OPG inhibits the differentiation and activity of osteoclasts by increasing the autophagy in vitro. Dietary supplementation of OPC can improve the growth performance of bone and alter the balance of osteoblasts and osteoclasts, thereby improving the bone health of chickens.

Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis.

Aim of the study: To investigate the anti-tumor effects of Lasiokaurin on breast cancer and explore its underlying molecular mechanism. Materials and methods: In this study, MTT assay, plate colony formation assays, soft agar assay, and EdU assay were employed to evaluate the anti-proliferation effects of LAS. Apoptosis and cell cycle distribution were detected by flow cytometry. The molecular mechanism was predicted by performing RNA sequencing and verified by using immunoblotting assays. Breast cancer organiods derived from patient-derived xenografts model and MDA-MB-231 xenograft mouse model were established to assess the effect of LAS. Results: Our study showed that LAS treatment significantly suppressed cell viability of 5 breast cancer cell lines, with the IC50 value of approximately 1-5 µM. LAS also inhibitied the clonogenic ability and DNA synthesis of breast cancer cells, Moreover, LAS induced apoptosis and G2/M cell cycle arrest in SK-BR-3 and MDA-MB-231 cells. Notably, transcriptomic analysis predicted the mechanistic involvement of PLK1 in LAS-suppressed breast cancer progression. Our experiment data further verified that LAS reduced PLK1 mRNA and protein expression in breast cancer, accompanied by downregulating CDC25C and AKT phosphorylation. Ultimately, we confirmed that LAS inhibit breast cancer growth via inhibiting PLK1 pathway in vivo. Conclusions: Collectively, our findings revealed that LAS inhibits breast cancer progression via regulating PLK1 pathway, which provids scientific evidence for the use of traditional Chinese medicine in cancer therapy.

Baicalin and N-acetylcysteine regulate choline metabolism via TFAM to attenuate cadmium-induced liver fibrosis.

(Background): Cadmium is an environmental pollutant associated with several liver diseases. Baicalin and N-Acetylcysteine have antioxidant and hepatoprotective effects. (Purpose): However, it is unclear whether baicalin and N-Acetylcysteine can alleviate Cadmium -induced liver fibrosis by regulating metabolism, or whether they exert a synergistic effect. (Study design): We treated Cadmium-poisoned mice with baicalin, N-Acetylcysteine, or baicalin+ N-Acetylcysteine. We studied the effects of baicalin and N-Acetylcysteine on Cadmium-induced liver fibers and their specific mechanisms. (Methods): We used C57BL/6 J mice, and AML12, and HSC-6T cells to establish in vitro assays and in vivo models. (Results): Metabolomics was used to detect the effect of baicalin and N-Acetylcysteine on liver metabolism, which showed that compared with the control group, the Cadmium group had increased fatty acid and amino acid levels, with significantly reduced choline and acetylcholine contents. Baicalin and N-Acetylcysteine alleviated these Cadmium-induced metabolic changes. We further showed that choline alleviated Cadmium -induced liver inflammation and fibrosis. In addition, cadmium significantly promoted extracellular leakage of lactic acid, while choline alleviated the cadmium -induced destruction of the cell membrane structure and lactic acid leakage. Western blotting showed that cadmium significantly reduced mitochondrial transcription factor A (TFAM) and Choline Kinase α(CHKα2) levels, and baicalin and N-Acetylcysteine reversed this effect. Overexpression of Tfam in mouse liver and AML12 cells increased the expression of CHKα2 and the choline content, alleviating and cadmium-induced lactic acid leakage, liver inflammation, and fibrosis. (Conclusion): Overall, baicalin and N-Acetylcysteine alleviated cadmium-induced liver damage, inflammation, and fibrosis to a greater extent than either drug alone. TFAM represents a target for baicalin and N-Acetylcysteine, and alleviated cadmium-induced liver inflammation and fibrosis by regulating hepatic choline metabolism.

Effectiveness of potato late blight (Phytophthora infestans) forecast by meteorological estimation in mountainous terrain based on CARAH rules.

Potato late blight (PLB) caused by Phytophthora infestans (Mont.) de Bary, its incidence and development are highly dependent on meteorological conditions. To solve the problem of PLB in mountainous terrain under the condition of limited meteorological monitoring capability, the air temperature and humidity was estimated based on the basic meteorological datasets, the forecast effect of the onset period and infection cycle of PLB based on CARAH rules was evaluated. The average MAE, RMSE and CI of the estimated air temperature and observations were 1.17 °C, 1.52 °C and 0.95, respectively. The average MAE, RMSE and CI of the estimated relative humidity and observations were 8.0 %, 10.7 % and 0.53, respectively. The curve of the infection cycle of PLB at different locations were estimated from the basic meteorological datasets based on the CARAH rules, and the false alarm and missing ratios were 8.8 % and 4.6 % respectively. It may be delayed by 1 or 2 fungal generations compared to the observations, and then the protective fungicide should be adjusted to a systemic fungicide. The false alarm of the infection cycle of PLB may increase in dry air conditions, and the missing report may occur in humid condition.

Functional Axis of PDE5/cGMP Mediates Timosaponin-AIII-Elicited Growth Suppression of Glioblastoma U87MG Cells.

Glioblastoma (GBM) is the most aggressive brain tumor, with high mortality. Timosaponin AIII (TIA), a steroidal saponin isolated from the medicinal plant Anemarrhena asphodeloides Bge., has been shown to possess anticancer properties in various cancer types. However, the effect of TIA on GBM is unknown. In this study, we reveal that TIA not only inhibited U87MG in vitro cell growth but also in vivo tumor development. Moreover, we found that the cause of TIA-induced cell growth suppression was apoptosis. When seeking to uncover antitumor mechanisms of TIA, we found that TIA diminished the expression of cGMP-specific phosphodiesterase 5(PDE5) while elevating the levels of guanylate cyclases (sGCß), cellular cGMP, and phosphorylation of VASPser239. Following the knockdown of PDE5, PDE5 inhibitor tadalafil and cGMP analog 8-Bro-cGMP both inhibited cell growth and inactivated ß-catenin; we reason that TIA elicited an antitumor effect by suppressing PDE5, leading to the activation of the cGMP signaling pathway, which, in turn, impeded ß-catenin expression. As ß-catenin is key for cell growth and survival in GBM, this study suggests that TIA elicits its anti-tumorigenic effect by interfering with ß-catenin function through the activation of a PDE5/cGMP functional axis.

[Clinical Study of San Wei Sheng Huo Decoction in the Treatment of Refractory Chemotherapy-Induced Thrombocytopenia].

Objective: To investigate the efficacy and safety of treating refractory chemotherapy-induced thrombocytopenia (RCIT) with San Wei Sheng Huo Decoction (SWSHD) as the main formula. Methods: A retrospective study was conducted and the data of RCIT patients treated with SWSHD as the main formula were collected. Changes in peripheral blood platelet (PLT) levels at different time points of treatment were examined and the significant effective rate (SER) and effective rate (ER) were analyzed. We measured the increase in peripheral blood PLT count before and after treatment, analyzed the differences in PLT count increase for different degrees of RCIT treatment, and evaluated the safety of the treatment. Results: A total of 35 cases of RCIT were included in the study. With SWSHD as the main treatment formula, the 2-week ER and SER were 74.29% and 14.29%, respectively, the 2-month ER and SER were 84.38% and 60.50, respectively, and the 1-year ER and SER were 92.31% and 80.77%, respectively. PLT count increased at all time points after treatment compared with that before treatment ( P<0.01). Subgroup analysis showed that, 2 months after treatment started, peripheral blood PLT counts increased by as much as 51.02×10 9L －1 in the severe RCIT group, higher than that of the moderate RCIT group at 36.58×10 9L －1 ( P<0.05), and the difference persisted until 1 year after the treatment. No obvious traditional Chinese medicine-related adverse reaction was observed during the treatment. Conclusion: SWSHD takes effect rapidly and its effect is long-lasting and stable. Furthermore, SWSHD has a more significant effect on severe RCIT.

A Brief Review of Natural Products with Urate Transporter 1 Inhibition for the Treatment of Hyperuricemia.

Hyperuricemia is a common disease caused by a high level of uric acid. Urate transporter 1 (URAT1) is an important protein and mediates approximately 90% of uric acid reabsorption. Therefore, the URAT1 inhibitor is a class of uricosuric medicines widely used in the clinic for the treatment of hyperuricemia. To find the new medicine with stronger URAT1 inhibition and lower toxicity, researchers have been exploring natural products. This study systematically summarizes the natural products with URAT1 inhibition. The results show that many natural products are potential URAT1 inhibitors, such as flavonoids, terpenoids, alkaloids, coumarins, stilbenes, and steroids, among which flavonoids are the most promising source of URAT1 inhibitors. It is worth noting that most studies have focused on finding natural products with inhibition of URAT1 and have not explored their activities and mechanisms toward URAT1. By reviewing the few existing studies of the structure-activity relationship and analyzing common features of natural products with URAT1 inhibition, we speculate that the rigid ring structure and negative charge may be the keys for natural products to produce URAT1 inhibition. In conclusion, natural products are potential URAT1 inhibitors, and exploring the mechanism of action and structure-activity relationship will be an important research direction in the future.

Antiviral activities of Polygonum perfoliatum L. extract and related phenolic acid constituents against hepatitis B virus.

Chronic hepatitis B virus (HBV) infection is an important public health problem. Polygonum perfoliatum L. is a traditional medicinal herb and has been reported to have pharmacological activities such as anti-inflammatory, antibacterial, and antiviral. In this study, the antiviral activities and mechanisms of Polygonum perfoliatum L. extract against HBV and the effective components were investigated. The results showed that the total extract of Polygonum perfoliatum L. reduced the levels of HBV e antigen (HBeAg) secretion and the viral covalently closed circular DNA (CCC DNA) formation, but had little or no negative effects on viral capsid assembly and pregenomic RNA packaging. Further fractionation showed that the water extract (WE) fraction exerted comparable anti-HBV activities with the total extract, especially in inhibiting the CCC DNA formation and HBeAg production, indicating that the effective antiviral components are mainly distributed in this fraction. Further study showed that the phenolic acids constituents, protocatechuic acid, and gallic acid, but not ethyl caffeate, which is reported enriched in the WE fraction, showed strong anti-HBV activities in inhibiting viral core DNA synthesis, CCC DNA formation, and HBeAg production. These results suggested that the Polygonum perfoliatum L. total extract and the related phenolic acids like protocatechuic acid and gallic acid could inhibit HBV replication and also indicated the potential utility of Polygonum perfoliatum L. and related constituents as sources of novel antivirals against HBV.

In vitro analysis of green synthesized copper nanoparticles using Chloroxylon swietenia leaves for dye degradation and antimicrobial application.

Green fabrication of copper nanoparticles (CuNPs) is an environmentally friendly and cost-effective method of synthesis for biomedical and bioremediation applications. In recent times, bacterial pathogens contaminating or affecting food and food crops pose the greatest threat to the food industry. In addition to this issue, synthetic dyes released from the textile and dyeing industries are polluting aquatic ecosystems and agricultural lands. The combined impact of these two factors is considered a major threat to life. Therefore, the use of CuNPs will provide an effective and long-term solution as an antibacterial and dye removing agent. The current study focuses on the synthesis of CuNPs using the leaf extract of Chloroxylon swietenia (C-CuNPs). The formation of a peak at 390 nm and a change in color from yellow to dark brown confirmed the synthesis of C-CuNPs. Subsequent synthesis at pH 9 was suitable for preparing C-CuNPs. Structural and chemical characterization of C-CuNPs was performed using Fourier Transfer Infra-Red (FTIR), X-ray diffraction (XRD), Dynamic Light scattering (DLS), and Scanning Electron Microscopy (SEM) analysis. The synthesized C-CuNPs possess a crystalline nature, a functional group that resembles C. swietenia, and are negatively charged and spherical in shape. C-CuNPs were tested against Congo red, Coomassie blue, and crystal violet and they showed complete degradation within 24 h under optimum conditions. Disk diffusion and broth dilution assay were used to test the antibacterial activity of C-CuNPs against Staphylococcus nepalensis, Staphylococcus gallinarum, Pseudomonasstutzeri,Bacillus subtilis, and Enterococcus faecalis. Therefore, the present study represents the first report on C-CuNPs' ability to degrade synthetic dyes and kill foodborne bacterial pathogens. Thus, the study has shed light on the potential of green synthesized CuNPs as bioremediation and packaging material in the future.

Biosynthesis of zirconium nanoparticles (ZrO2 NPs) by Phyllanthus niruri extract: Characterization and its photocatalytic dye degradation activity.

The present study focused on microwave assisted synthesis of zirconium nanoparticles (ZrO2NPs) using leaf extract of Phyllanthus niruri as ecofriendly approach and assessed its antimicrobial and bioremediation efficiency. Visual color transition from yellow to brown indicates the formation of ZrO2NPs which was further substantiated by UV-Visible absorption peak at 300 nm. Dynamic Light Scattering (DLS) analysis revealed that the average particle size of ZrO2NPs as 121.5 nm with negative zeta potential of -22.6 mv. Scanning electron microscopic analysis showed spherical shaped nanoparticles with an average size of 125.4 nm. Results of photocatalytic studies revealed that ZrO2NPs exhibited 74%, 62% and 57%, dye degradation for methyl red, methyl orange, and methyl blue respectively. Antimicrobial studies depicted that ZrO2NPs exhibited bactericidal activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Aspergillus niger at dose of 200 µg/mL. Overall results of the present study revealed biogenic synthesis of ZrO2 NPs with potent bioremediation and antimicrobial properties.

Eco-friendly, green synthesized copper oxide nanoparticle (CuNPs) from an important medicinal plant Turnera subulata Sm. and its biological evaluation.

In this report, the green fabrication of copper oxide nanoparticles (CuNPs) using Turnera subulata leaf extract and assessed for the antibacterial and photocatalytic activities. The synthesis of CuNPs was performed using the leaves of T. subulata (TS-CuNPs) and characterized using UV-visible spectrophotometry, Fourier transforms infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), and Energy-dispersive X-ray spectroscopy (EDX). Produced TS-CuNPs showing transmittance peaks approximately 707-878 cm-1, with a spherical shape particle with an average size of 58.5 nm. As synthesized TS-CuNPs were used as a coating material in cotton fabrics and tested the efficacy against Gram-negative and Gram-positive bacterial pathogens. TS-CuNPs inhibited the growth of Escherichia coli and Staphylococcus aureus on cotton fabrics. Antibiofilm activity of TS-CuNPs showed a 4-fold reduction in the biofilm formation of E. coli and S. aureus. Structural morphology of TS-CuNPs coated on cotton fabric analysis using SEM-EDX confirmed the attachment of TS-CuNPs and reduction in the bacterial attachment to the cotton fabrics. Thus, this study provides a potential strategy to improve the antibacterial property of cotton fabrics in textile production for medical, sportswear, and casual wear applications. Further, the photocatalytic activity against the tested dyes evident the potential in dye industry wastewater treatment. Hence, this work represents a simple, greener, and cost-effective route for in situ synthesis of CuNPs with the potential antibacterial and as a dye degradation agent for water remediation.

Facile synthesis of biogenic palladium nanoparticles using biomass strategy and application as photocatalyst degradation for textile dye pollutants and their in-vitro antimicrobial activity.

Among biological applications, plant-mediated Pd NPs for multi-drug resistance (MDR) developed in pathogenic bacteria were synthesized with the help of biomass of lemon peel, a biological material, with a non-toxic, environmentally friendly, human-nature green synthesis method. Characterization of synthesized Pd NPs was carried out by UV-Vis spectrometry, Transmissive Electron Microscopy (TEM), X-ray diffraction (XRD), and Fourier Transform Infrared Spectroscopy (FTIR) techniques. According to TEM analysis, Pd NPs were confirmed to be in a spherical shape and the mean particle size was determined to be 4.11 nm. The crystal structure of Pd NPs was checked using XRD analysis and the mean particle size was observed to be 6.72 nm. Besides, the antibacterial activity of Pd NPs was determined against Escherichia coli (E. coli) (ATCC 8739), Bacillus subtilis (B. subtilis ATCC 6633), Staphylococcus aureus (S. aureus ATCC 6538), Klebsiella pneumoniae (K. pneumoniae ATCC 11296) and Serratia marcescens (S. marcescens ATCC) bacteria. Antibacterial activity was determined to be high in Pd NPs which is in conformance with the results acquired. The Pd NPs showed good photocatalytic activity, after 90 min illumination, about 81.55% and 68.45% of MB and MO respectively were catalysed by the Pd NPs catalyst, and 74.50% of RhB dyes were removed at 120 min of illumination. Within the scope of this project, it is recommended to use Pd NPs obtained by the green synthesis in the future as an antibacterial agent in biomedical use and for the cleaning of polluted waters.

Electrical Dry Needling Plus Corticosteroid Injection for Osteoarthritis of the Knee: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA). DESIGN: A prospective, single-blinded, randomized controlled trial. SETTING: Pain treatment clinic. PARTICIPANTS: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group. INTERVENTIONS: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN. MAIN OUTCOMES MEASURES: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data. RESULTS: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better). CONCLUSION: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation.

[Nucleic acid aptamer-based traditional Chinese medicine application:therapy,targeting and diagnosis].

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.

Quercetin and Allicin Can Alleviate the Hepatotoxicity of Lead (Pb) through the PI3K Signaling Pathway.

Lead (Pb) is a common toxic heavy metal pollutant in the environment that seriously endangers the health of animals. The liver is a key target organ affected by Pb toxicity. Plant extracts allicin and quercetin have a strong antioxidant capacity that can promote the excretion of heavy metals by improving the body's antioxidant defense and chelating heavy metal ions. To explore the preventive and therapeutic effects of allicin and quercetin on Pb poisoning in chickens, 96 chickens were randomly divided into eight groups: control, Pb, allicin, quercetin, allicin + quercetin, Pb + allicin, Pb + quercetin, and Pb + allicin + quercetin groups. The chickens were given feed containing the above treatments for 90 days. The results indicated that Pb can affect the growth and development of the liver, damage the circulatory system, destroy the structure of mitochondria and nuclei in liver cells, cause an imbalance in the oxidation system, inhibit PI3K protein, and activate the mitochondrial apoptotic pathway. Allicin and quercetin, alone or in combination, can improve the antioxidant capacity of the liver and alleviate liver tissue damage caused by Pb. In summary, allicin and quercetin could alleviate oxidative damage and apoptosis in the Pb-poisoned chicken liver through the PI3K signaling pathway, with stronger effects achieved by their combination.

Mechanism underlying Polygonum capitatum effect on Helicobacter pylori-associated gastritis based on network pharmacology.

Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.

Puerarin Restores Autophagosome-Lysosome Fusion to Alleviate Cadmium-Induced Autophagy Blockade via Restoring the Expression of Rab7 in Hepatocytes.

Autophagic dysfunction is one of the main mechanisms by which the environmental pollutant cadmium (Cd) induces cell injury. Puerarin (Pue, a monomeric Chinese herbal medicine extract) has been reported to alleviate Cd-induced cell injury by regulating autophagy pathways; however, its detailed mechanisms are unclear. In the present study, to investigate the detailed mechanisms by which Pue targets autophagy to alleviate Cd hepatotoxicity, alpha mouse liver 12 (AML12) cells were used to construct a model of Cd-induced hepatocyte injury in vitro. First, the protective effect of Pue on Cd-induced cell injury was confirmed by changes in cell proliferation, cell morphology, and cell ultrastructure. Next, we found that Pue activated autophagy and mitigated Cd-induced autophagy blockade. In this process, the lysosome was further activated and the lysosomal degradation capacity was strengthened. We also found that Pue restored the autophagosome-lysosome fusion and the expression of Rab7 in Cd-exposed hepatocytes. However, the fusion of autophagosomes with lysosomes and autophagic flux were inhibited after knocking down Rab7, and were further inhibited after combined treatment with Cd. In addition, after knocking down Rab7, the protective effects of Pue on restoring autophagosome-lysosome fusion and alleviating autophagy blockade in Cd-exposed cells were inhibited. In conclusion, Pue-mediated alleviation of Cd-induced hepatocyte injury was related to the activation of autophagy and the alleviation of autophagy blockade. Pue also restored the fusion of autophagosomes and lysosomes by restoring the protein expression of Rab7, thereby alleviating Cd-induced autophagy blockade in hepatocytes.

Behavior of Nutritional Supplements Use in Association With Inflammatory Skin Diseases in Chinese College Students.

Objectives: It is understudied how frequently adolescents use nutritional supplements (NS) and whether the corresponding behavior is associated with skin diseases that may cause unpleasant symptoms and disfigurement. The current study aimed to investigate the prevalence of NS use in Chinese college students and its association with inflammatory skin diseases. Methods: This was a university-based epidemiologic investigation that included 20,138 students who underwent dermatological examinations. A questionnaire survey was conducted to inquire about the use of NS along with related information. Skin diseases were diagnosed by dermatologists during the health examination. Logistic regression models were used for analysis. Adjusted odds ratios (aORs) were presented as the effect size. Results: Survey responses from a total of 20,138 participants were analyzed. Specifically, 18.3% of the participants reported the use of NS in the past year. The use of vitamin C was most frequently reported, accounting for a proportion of 12.9%, followed by vitamin B and mineral supplements. The use of NS was found to be associated with female sex, Han ethnicity, higher annual household income, and a series of healthy lifestyles such as more physical activity, less second-hand smoke exposure, less alcohol consumption, and higher intake of milk and yogurt (p < 0.001). Participants with chronic urticaria (aOR = 1.3; 95% CI, 1.0-1.7), atopic dermatitis (aOR = 1.4; 95% CI, 1.2-1.6), or acne (aOR = 1.17; 95% CI, 1.04-1.31) were more likely to use NS, especially herbs (aOR = 2.7; 95% CI, 1.2-3.7), followed by vitamin B (aOR = 1.6; 95% CI, 1.2-2.0) and mineral supplements (aOR = 1.4; 95% CI, 1.0-2.0). Conclusion: College students with inflammatory skin diseases are more likely to use NS.

Alpha-Lipoic Acid Attenuates Cadmium- and Lead-Induced Neurotoxicity by Inhibiting Both Endoplasmic-Reticulum Stress and Activation of Fas/FasL and Mitochondrial Apoptotic Pathways in Rat Cerebral Cortex.

Although many studies have reported toxic effects of cadmium (Cd) and lead (Pb) in the central nervous system, few studies have investigated the combined toxicity of Cd and Pb. The mechanisms by which these combined heavy metals induce toxicity, as well as effective means to exert neuroprotection from these agents, remain poorly understood. To investigate the protective effects of alpha-lipoic acid (α-LA) on Cd- and/or Pb-induced cortical damage in rats, 48 Sprague-Dawley rats were exposed to drinking water containing 50 mg/L of Cd and/or 300 mg/L of Pb for 12 weeks, in the presence or absence of α-LA co-treatment (50 mg/kg) via gavage. We observed that exposure to Cd and/or Pb decreased the brain weight/body weight ratio and increased Cd and/or Pb contents as well as ultrastructural damage to the cerebral cortex. Cd and/or Pb also induced endoplasmic-reticulum (ER) stress and activated Fas (CD95/APO-1)/Fas ligand (FasL) and mitochondrial apoptotic pathways. Furthermore, co-treatment of Cd and Pb further exacerbated part of these phenotypes than treatment of Cd or Pb alone. However, simultaneous supplementation with α-LA attenuated Cd and/or Pb-induced neurotoxicity by increasing the brain weight/body weight ratio, reducing Cd and/or Pb contents, ameliorating both nuclear/mitochondrial damage and ER stress, and attenuating activation of Fas/FasL and mitochondrial apoptotic pathways. Collectively, our results indicate that the accumulation of Cd and/or Pb causes cortical damage and that α-LA exerts protection against Cd- and/or Pb-induced neurotoxicity. These findings highlight that α-LA may be exploited for the treatment and prevention of Cd- and/or Pb-induced neurotoxicity.

Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection.

BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.